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Biomedical subjects

A Linde

Publications and source records attributed to A Linde.

At least 73 records · Page 4Linked to original sources
PubMed1999

Reactivation of human herpesvirus 6 during pregnancy.

Reactivation of human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) during pregnancy and transmission of the viruses to the fetus were investigated by polymerase chain reaction (PCR) and serology. In all, 104 blood samples were obtained 3 times during pregnancy and once at delivery. In another 107 women, samples were obtained only at delivery. Cord blood samples were obtained from both groups of women. HHV-6 DNA was detected in 41%-44% of the samples during months 3-8 of pregnancy, in 25% at delivery, and in 24% of age-matched controls. HHV-6 DNA was found in 1.0% of the cord blood samples. CMV DNA was detected in 1.7% of leukocytes from 104 pregnant women but in no cord blood sample. IgG antibodies to HHV-6 were found in 96% and CMV IgG in 62.5% of the women. HHV-6 IgG titers were significantly higher in HHV-6 PCR-positive women. Thus, HHV-6 reactivation seems common during pregnancy, and transfer of HHV-6 to the fetus may occur in approximately 1% of pregnancies.

Adult↗
PubMed1999

Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy.

A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.

Adult↗
PubMed1999

Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance?

Cerebrospinal fluid (CSF) specimens from 22 allogeneic bone marrow transplant patients with central nervous system (CNS) symptoms (cases) and 107 patients who were immunocompromised but did not have CNS symptoms (controls) were assayed for human herpesvirus 6 (HHV-6) DNA. HHV-6 DNA was detected in CSF specimens from five (23%) of 22 cases and in CSF specimens from one (0.9%) of 107 controls (P < .001, Fisher's exact test). In addition, none of the five cases with HHV-6 DNA detected in CSF samples had any other identified cause of their CNS symptoms, and none of the other 11 cases with known causes for their CNS diseases had HHV-6 DNA detected in CSF samples (P = .03, Fisher's exact test). In three cases, HHV-6 variant B was identified, and the HHV-6 variant could not be defined in the other two cases. Prophylaxis with acyclovir did not prevent the occurrence of HHV-6-associated CNS disease after allogeneic bone marrow transplantation. Four cases' conditions were improved or they were cured after treatment with either ganciclovir or foscarnet, and one case died of CNS disease despite foscarnet treatment.

Adult↗
PubMed1999

Bone neogenesis in domes made of expanded polytetrafluoroethylene: efficacy of rhBMP-2 to enhance the amount of achievable bone in rats.

For bone reconstructive purposes, it would be a great advantage to be able to gain bone without grafting. In experimental studies, barrier membranes have been used to accomplish this, however, with limited efficacy. In this study, the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the early onset of bone formation, as well as on the final amount of achievable bone, was investigated in an experimental osteo-neogenesis model. In 60 adult rats, dome-shaped barrier membranes made of expanded polytetrafluoroethylene (Gore-Tex membrane), with an inside volume of approximately 60 mm3, were placed on the left parietal bone. The domes were pretreated according to four different alternatives: (1) filled with autogenous blood only (n = 15); (2) filled with 5 microg of rhBMP-2 in an absorbable collagen sponge carrier (n = 15); (3) filled with 15 microg of rhBMP-2 in absorbable collagen sponge carrier (n = 15); or (4) filled with the absorbable collagen sponge carrier only (n = 15). The animals treated according to each alternative were then divided into three equal groups with five rats in each, and subsequently killed after 3, 6, or 12 weeks. The amount of bone formed within the domes was evaluated by light microscopy and computer-assisted image analysis. It was found that the amount of newly formed bone could be enhanced by approximately 100 percent by simultaneous implantation of rhBMP-2, irrespective of dose. The early onset of bone formation was, however, not affected by the rhBMP-2 supplementation. This finding was interpreted as being due to the delivery system used, because as long as the carrier was still present, no significant difference between the treatment groups was observed. The bone formed in domes with carrier implantation, with or without rhBMP-2, displayed more marrow spaces in comparison to controls. The combined treatment with barrier membranes and local delivery of rhBMP-2 may be a useful tool in reconstructive surgery, for instance replacing onlay grafting, especially when a more delicate anatomy is necessary, because membranes can be shaped in multiple ways.

Animals↗
PubMed1999

Effects of rhBMP-2 and osteopromotive membranes on experimental bone grafting.

A problem with using autogeneic bone for onlay grafting is its degree of incorporation and volumetric persistence. This study explored whether improved graft volumetric maintenance can be achieved by recombinant human bone morphogenetic protein-2 (rhBMP-2) and whether a combination of rhBMP-2 and osteopromotive membranes is advantageous in this respect. Unicortico-cancellous bone grafts were positioned below the temporal muscle bilaterally in 48 adult Lewis rats. The recipient bone was ground, and the grafted area was randomly treated according to one of eight different alternatives. Two doses of rhBMP-2 (4 microg/80 microl or 32 microg/80 microl buffer) in a collagenous carrier were tested, with or without coverage with expanded polytetrafluoroethylene membranes. As controls, membrane and carrier, alone or in combination, and onlay grafts only were used. The results were evaluated after 4 and 20 weeks by routine histologic examination and immunohistochemical labeling for various bone and cartilage matrix proteins. After 4 weeks, rhBMP-2-treated grafts showed complete integration, whereas for controls, only the membrane-alone group attained incorporation after 20 weeks. The combined treatment with high-dose rhBMP-2 and membrane demonstrated, as compared with the remaining rhBMP-2 groups, pronounced bone formation and less graft resorption, resulting in maintained or increased graft size. This was observed after 4 weeks, and the result remained at 20 weeks. Treatment with high-dose rhBMP-2 without membrane placement, in contrast, resulted in extensive resorption and graft size reduction at 20 weeks. Control groups showed less success in graft size persistence. It was concluded that a combination of high-dose rhBMP-2 and osteopromotive membranes had a synergistic effect, leading to rapid, complete graft integration and size maintenance. In the absence of a membrane, the protein seemed to accelerate the remodeling of the graft.

Animals↗
PubMed1999

Similar humoral and cellular immunological reactivities to human herpesvirus 6 in patients with multiple sclerosis and controls.

Several studies have suggested an association between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS). We have previously studied intrathecal production of antibody to lymphotropic herpesviruses in MS patients and the presence of human herpesvirus 1 to 7 DNAs in cerebrospinal fluid (CSF). In the present study anti-HHV-6 immunoglobulin M (IgM) in serum and anti-HHV-6 IgG subclasses in serum and CSF were examined and the lymphoproliferative response to HHV-6 was analyzed. The PCR examination was refined by purifying DNA from CSF and retesting the samples for HHV-6 DNA. There were no statistically significant differences between the groups concerning IgM positivity, distribution of IgG subclasses, or lymphoproliferative response to HHV-6. The purification of DNA increased the number of PCR-positive samples from 0 of 71 to 4 of 68. The study does not give additional support to the possibility that HHV-6 is a common cause of MS, but a role for the virus in a subset of patients cannot be excluded.

Adolescent↗
PubMed1999

Human herpesvirus 6 in cerebrospinal fluid of patients infected with HIV: frequency and clinical significance.

The objective was to evaluate the frequency of human herpesvirus 6 (HHV-6) DNA detection in the CSF of patients infected with HIV and its relation to brain disease and systemic HHV-6 infection. Nested polymerase chain reaction (PCR) was used to analyse CSF samples from 365 consecutive HIV infected patients with neurological symptoms. When available, plasma and brain tissues from patients whose CSF was HHV-6 positive were also studied. HHV-6 was found in the CSF of eight of the 365 patients (2.2%): two had type A and four type B; the HHV-6 variant could not be defined in the remaining two. All eight patients had neurological symptoms and signs related to concomitant opportunistic brain diseases, including cytomegalovirus (CMV) encephalitis in five patients whose CSF was also positive for CMV-DNA. Opportunistic infections but no other unexplained lesions were also found in the brain of all of the four patients who underwent neuropathological examination. Both HHV-6 and CMV were also detected in the plasma of respectively five and seven of seven patients whose CSF was HHV-6 positive. In conclusion, HHV-6 type A or B DNA was infrequently found in the CSF of HIV infected patients, in association with both CMV brain infection and systemic HHV-6 replication. However, no certain relation between HHV-6 and brain disease was found.

Adult↗
PubMed1999

Elevated antibody levels to Epstein-Bbarr virus antigens in patients with hairy cell leukemia compared to controls in relation to exposure to pesticides, organic solvents, animals, and exhausts.

Epstein-Barr virus (EBV) is a B-lymphotropic human herpes virus infecting B-cells, which has been associated with lymphoid malignancies, above all non-Hodgkin lymphomas (NHL). Severe immunosuppression is the best recognized risk factor for NHL. Many factors in the environment that have been described as risk factors for NHL cause measurable changes in immune functions. Hairy cell leukemia (HCL) is a rare, indolent non-Hodgkin lymphoma, originating from B-lymphocytes. This was a case-control study including 111 male cases with HCL and 400 controls. In a subgroup of 57 cases and 65 controls analysis of antibodies to EBV early antigen, viral capsid antigen, and EBNA-1, measured as P107, was performed. In this study, we confirm other studies describing elevated levels of antibodies to the EBV early antigen (EA) in patients with HCL compared to controls. We found only minor differences in the levels of antibodies to the viral capsid antigen (VCA) and EBNA-1. measured as P107. We found a positive association of a titer to EA IgG > or =40 (OR 4.1; CI 1.9-9.5). The ORs were further elevated when subjects with high levels of EA IgG and exposed to environmental agents such as organic solvents, certain pesticides, impregnating agents, animals, and exhausts were compared to those subjects with low levels that were not exposed. Antibody reactivity against the EBV EBNA 1-alanine-glycine repeat (P107 IgG) above the median gave an increased OR for HCL, which further increased in subjects exposed to organic solvents, certain pesticides. impregnating agents, animals, and exhausts. However, the numbers of exposed cases and controls were small in some of the calculations.

Air Pollution↗
PubMed1999

Lymphoproliferative responses to human herpesvirus-6 variant A and variant B in healthy adults.

Human herpesvirus-6 (HHV-6) isolates can be classified into variants A and B, and over 95% of people older than 2 years of age are seropositive for either or both variants. However, the prevalence of the two HHV-6 variants is still not defined since the serological methods used at present cannot discriminate one variant from the other. Lymphoproliferative responses to glycine extracted cellular antigens from human herpes-virus-6 (HHV-6) GS strain (variant A)- and Z 29 strain (variant B)-infected T-lymphoid cell lines were examined in healthy Swedish and Japanese adults. Nine of 36 (25%) persons had responses to the GS antigen, while 21/36 (58%) had responses to the Z 29 antigen (P=0.008). Individuals with low anti-HHV-6 IgG titers (< or = 320) were more likely to respond to the Z 29 antigen than to the GS antigen (P=0.006), while there was no difference in those with high anti-HHV-6 IgG titers (> or =1280). Three of 7 Japanese adults had lymphoproliferative responses to the GS antigen compared with 6/29 Swedes (not significant), and 7/7 Japanese had lymphoproliferative responses to the Z 29 antigen compared with 14/29 Swedes (P=0.03). Lymphoproliferative responses were neither related with the presence of HHV-6 DNA nor related with the presence of HHV-7 DNA in peripheral blood cells. These results suggest a higher prevalence of HHV-6 variant B than variant A in both Swedes and Japanese adults, and possibly a difference in either the HHV-6 virus strains and/or the nature of immune response of Swede and Japanese.

Adult↗
PubMed1998

Modulation of rat incisor odontoblast plasma membrane-associated Ca2+ with nifedipine.

In addition to the Ca2+ portion freely dissociated in the cytosol, another Ca2+ pool is associated with plasma membranes and intracellular organelle membranes. This Ca2+ portion is of importance for regulation of, among other things, the cell cycle, actin-mediated processes, and cell morphology. In the literature, dihydropyridines have been reported to influence this membrane-associated pool of Ca2+ under certain conditions. The aim of this investigation was to study possible modulations of plasma membrane-associated Ca2+ upon treatment with nifedipine in vitro in a Ca2+-transporting cell, the dentin-forming odontoblast. The membrane-associated portion of Ca2+ in dissected dentinogenically active rat incisor odontoblasts was monitored by fluorescence spectrophotometry using chlortetracycline as a probe. In addition, images of chlortetracycline-Ca2+ binding were obtained by fluorescence microscopy. It was found that membrane-associated Ca2+ decreased by the dihydropyridine nifedipine, whereas this Ca2+ pool was unaffected by the cellular polarization state, which was in contrast to cytosolic free Ca2+ as measured by fura-2. The results show that the odontoblast plasma membrane-associated Ca2+-pool can be modulated by nifedipine, thus being dependent on the conformational state of the L-type Ca2+ channels.

Animals↗
PubMed1998

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation.

A nested polymerase chain reaction (nPCR) for Epstein-Barr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30% and RNA in 34% of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods (P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90% of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-immunoblastic infiltrates, either in nPCR (P = 0.73) or in ISH (P = 0.73). Two of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBV-nPCR but negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention.

Adolescent↗
PubMed1998

Parathyroid hormone (1-34) receptor-binding and second-messenger response in rat incisor odontoblasts.

Even though indirect evidence indicates that PTH exerts an anabolic effect on dentinogenesis, the existence of PTH receptors and any second-messenger response in odontoblasts have not been demonstrated. The aim of this study was to investigate whether rat incisor odontoblasts express PTH receptors, and to identify which second messenger pathway the hormone may activate. Odontoblasts were dissected from rat incisors. Amino-terminal (1-34) fragment rat PTH [rPTH(1-34)] conjugated to fluorescein isothiocyanate visualized receptor sites on the cell surface. Upon incubation of odontoblasts with rPTH(1-34), cAMP formation was increased. However, no fluctuations in intracellular calcium activity were observed upon rPTH(1-34) stimulation when using Fura-2 as a Ca2+ probe. In long-time incubations, stimulation with PTH(1-34) upregulated APase activity. The results demonstrate that rPTH(1-34) evokes an anabolic response in dentinogenically active odontoblasts, and that this may be mediated through the protein kinase A/cAMP pathway, whereas no indications for Ca2+ as a second messenger were evident.

Alkaline Phosphatase↗
PubMed1998

Solid phase ELISA for determination of the virus dose dependent sensitivity of human cytomegalovirus to antiviral drugs in vitro.

The main problems in determining the true in vivo susceptibility of human cytomegalovirus (CMV) to antiviral compounds are the influence of the size of the viral inoculum, the variation in the replication capacity of different CMV strains and the subjective evaluation of the inhibition of viral growth in the plaque assay. In this study, a specific assay was developed which reproducibly determines the sensitivity of primary isolates of CMV. The assay includes simultaneous virus titration and determination of the antiviral sensitivity. When individual virus doses were evaluated, the IC50 was generally dependent on the virus dose, except for resistant isolates, where the IC50 did not change irrespective of the dose of virus. The novel method of IC50 calculation takes into account all values derived from the linear part of the inhibition curve. This may better reflect the in vivo conditions, where the antiviral drug encounters different amounts of virus in different organs. Two human fibroblast-derived cell lines showed similar results.

Antiviral Agents↗
PubMed1998

Osteopromotive membranes enhance onlay integration and maintenance in the adult rat skull.

This study aimed to evaluate the effect of an osteopromotive membrane technique on onlay bone graft survival. Unicortical bone grafts were positioned bilaterally below the temporal muscle in 21 adult Lewis rats. In 14 rats, the bone graft on the right side was covered by an expanded polytetrafluoroethylene GORE-TEX membrane, whereas that on the left side was left uncovered. Seven rats were killed after 12 (group 1) and 20 (group 2) weeks, respectively. The remaining animals (n = 7, group 3) received membranes bilaterally, of which the right-sided membrane was removed after 12 weeks, and these animals were killed after 20 weeks. The specimens were assessed by routine histology and immunohistochemical labelling for various matrix proteins. After 12 weeks (group 1), size differences between the sides were not significant, although all control onlay bone grafts showed microscopic signs of pronounced resorption. At 20 weeks (group 2), graft integration was more complete on the membrane side. For group 3, the height was significantly more preserved on the side where the membrane was not removed. Immunolabelling demonstrated a more intense bone remodelling at the membrane sites. Membrane treatment resulted in improved graft integration and significantly greater size persistence, but complete height was not maintained.

Animals↗
PubMed1998

Importance of bone graft quality for implant integration after maxillary sinus reconstruction.

OBJECTIVE: The aim of this study was to determine whether bone quality, as assessed by osteometry and histologic parameters, can be used to predict implant integration in conjunction with maxillary sinus reconstruction. STUDY DESIGN: Twelve patients with severely atrophied maxillary alveolar processes were treated through use of a two-stage surgical reconstructive strategy with implant placement 4 months after bone grafting. Bone biopsy specimens taken from the iliac crest peroperatively and from the sinus inlay sites 1, 2, 4, 6, or 12 months postoperatively were analyzed by light microscopy and osteomorphometry. Bone mineral content was measured by osteometry. RESULTS: Osteometric and osteomorphometric data (trabecular bone volume [%], assessment of chromatin staining, and an osteocyte index) registered for the biopsy specimens were not statistically correlated with implant failure. CONCLUSIONS: Prognostic evaluation of implant survival is difficult. The tested methods did not contribute to the improvement of guidelines for the clinical handling of these patients.

Adult↗
PubMed1998

Immunoglobulin G abnormalities in HIV-1 infected individuals with lymphoma.

BACKGROUND: Polyclonal B-cell activation precedes the occurrence of malignant B-cell clones. Several recent reports suggest a perturbed cytokine regulation in HIV-related lymphomagenesis and Epstein-Barr virus (EBV) involvement in approximately half of the cases with generalized lymphoma. OBJECTIVES: We investigated whether altered immunoglobulin properties would be detected by fine analysis of the immunoglobulin G (IgG) subclass patterns against HIV and EBV epitopes. STUDY DESIGN: HIV-1 infected patients in early stage, late stage and with lymphoma were analyzed by ELISA for anti HIV and EBV IgG class and subclass antibodies. Avidity and affinity of the antibodies were studied. The lymphoma patients were also studied by PCR for EBV DNA in serum. RESULTS: The total IgG reactivity to several HIV antigens was similar in the three patient groups. However, lymphoma patients had a more restricted subclass pattern with significantly lower IgG1 and IgG3 anti gp120 titers compared to other HIV-infected patients but good and persistent total IgG and IgG1 (excluding the gp120 antigen) reactivities in contradiction to their low CD4 counts. IgG4 reactivity was sparse, detectable to significant levels in the symptomatic group only. The observed relative affinity of the HIV-specific IgG and IgG1 of lymphoma patients was similar to that of asymptomatic and symptomatic patients. The subclass reactivity to the EBV peptide was similar in all groups but lymphoma patients with EBV DNA in serum exhibited significantly lower anti EBV peptide titers than those who were EBV DNA negative. CONCLUSION: These findings indicate that subclass analysis to defined viral antigens may be a means to detect immune dysregulation in tumor development.

Antibody Affinity↗