[Time to vaccinate against influenza. We have not reached the target last year].
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Cost-Benefit Analysis↗
Biomedical subjects
A Linde
Publications and source records attributed to A Linde.
Epstein-Barr virus and cytomegalovirus in relation to testicular-cancer risk: a nested case-control study.
An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.
Adult↗
Nosema portugal, N. SP., isolated from gypsy moths (Lymantria dispar L.) collected in portugal
A microsporidium Nosema portugal n. sp. was isolated from gypsy moths, Lymantria dispar L, collected near Lisbon, Portugal, in 1985. The life cycle includes two sequential developmental cycles, a primary and a secondary cycle. The primary cycle occurs in midgut epithelial cells, where primary spores are produced within 48 h. The primary spores immediately extrude their polar filaments, presumably to infect other cells. In the target tissues (salivary glands and fat body) the secondary development cycle is followed by the formation of environmental spores. Primary spores were also sometimes present in target tissues. Fresh unfixed and unstained primary spores have a large posterior vacuole and measured 4.8 x 2.7 &mgr;m. Ultrastructurally, they have 5-8 polar filament coils, a large posterior vacuole, abundant endoplasmic reticulum, and were binucleate. Mature unfixed and unstained environmental spores were highly refractive and the posterior vacuole and nuclei could not be seen through the spore coat. Fresh environmental spores measured 4.5 x 1.9 &mgr;m. Ultrastructurally, environmental spores were binucleate, with a typical polaroplast, 10-11 isofilar polar filament coils, and a series of 4-6 thin polar filament-like tubules situated at the posterior end of the row of typical polar filament coils. The ssu rRNA sequences strongly suggest that this species is more closely related to the Vairimorpha subgroup within the Nosema/Vairimorpha clade than to the Nosema subgroup. Copyright 1999 Academic Press.
Journal Article↗
Subsets of T-cells and in vitro cytokine production after measles and varicellae-zoster virus antigen stimulation in allogeneic BMT patients.
This study was performed to analyse differences in T-cell proliferation induced by a latent virus, varicellae-zoster virus (VZV) and a non-latent virus, measles virus, in patients after allogeneic bone marrow transplantation (BMT). The lymphoproliferative response to measles antigen, VZV-antigen (VZV-ag), and phytohemagglutinin (PHA) was measured by 3H-thymidine incorporation, and interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) analyses in supernatants after in vitro stimulation of peripheral blood mononuclear cells (PBMC) from 22 patients and 18 healthy controls. The cytokine levels were correlated with T-cell subsets by FACS analyses. At the antigen concentrations used, VZV-ag induced higher levels of IFN-gamma (p < 0.05) than did the measles antigen, whereas the levels of IL-10 were similar. Patients without a cell mediated immune (CMI) response to VZV-ag or measles antigen had lower CD4+ T-cell counts than did controls (p < 0.01 in both cases) and lower IFN-gamma production after non-specific PHA stimulation (p <0.01). The IFN-gamma and IL-10 levels after measles antigen stimulation correlated with the number of CD4+ T-cells (p < 0.01 and p < 0.05, respectively), and after VZV-ag mainly to the number of CD8+ T-cells (p < 0.01 and p < 0.05, respectively). These results suggest that there is a difference in the types of T-cells that respond to VZV-ag and measles antigen stimulation, respectively. The impaired CMI response to viral antigens seen in many patients may be explained both by a low number of CD4+ T-cells and by a cell dysfunction.
Adult↗
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↗
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↗
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↗
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↗
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↗
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↗
[Why should all persons over age 65 years be vaccinated against influenza?].
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Age Factors↗
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↗
[Can fowl influenza in Hong Kong cause a pandemic? Increased alertness is justified, the danger is not yet over].
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Animals↗
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↗
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↗
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↗
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↗
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↗