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Biomedical subjects

B Wahren

Publications and source records attributed to B Wahren.

At least 307 records · Page 17Linked to original sources
PubMed1985

Cytomegalovirus DNA polymerase inhibition and kinetics.

Cytomegalovirus (CMV) DNA polymerase has immunologic specificity in relation to the virus specific polymerases of other herpesviruses. During the early phase of CMV infection in vitro, the virus DNA polymerase is rapidly induced. Due to the lack of virus specific thymidine kinase, cytomegalovirus is resistant to nucleosides which require herpesvirus thymidine kinases for activation. Cytomegalovirus DNA polymerase is therefore the known possible target for antiviral drugs. Several pyrophosphate analogs have been assayed for their inhibitory effects on this enzyme. The most active compound is phosphonoformate (PFA). PFA also effectively inhibits other partially purified herpesvirus DNA polymerases as well as the multiplication of all human herpesviruses, at concentrations which do not affect cellular DNA polymerases or normal cell growth. The mechanism of inhibition is a noncompetitive inhibition of CMV DNA polymerase activity with respect to the four deoxyribonucleoside triphosphates, and an uncompetitive inhibition with respect to the template used. In cell culture, PFA inhibits the formation of late CMV polypeptides, but not the synthesis of early CMV polypeptides. The CMV specific polymerase persists in the presence of PFA, as measured by immunological methods, and enzyme activity can be demonstrated after removal of PFA. The inhibition of CMV replication is reversible even after long exposure to PFA. Our interpretation is that the CMV genome is highly resistant to the cellular metabolism also in non-producing cells. A new rapid CMV neutralization test was established, based on the appearance of early CMV-induced antigens.

Antigens, Viral↗
PubMed1985

Sensitive analytic ELISAs for subclass herpes virus IgG.

The subclass distribution of antiviral antibodies to three herpes viruses was studied in a population of healthy blood donors. Subclassification by monoclonal antibodies led to the identification of certain viral IgG patterns. IgG1 appeared to be formed in response to almost all CMV, HSV-1 and VZV infections. A higher frequency of virus-specific IgG3 to CMV and HSV-1 suggested that these infections may be reactivated subclinically more often than VZV. The presence of CMV and VZV IgG4 showed a familial relationship, while IgG4 responses to HSV-1 were common. Persons with IgG4 as the only subclass-reactive antibody to CMV showed cell-related reactivities in a high frequency. Patients with leukemias, myelomas and Crohn's disease had a near-normal subclass pattern to the herpes viruses.

Antibodies, Viral↗
PubMed1985

Lymphocyte proliferation and IgG production with herpesvirus antigens in solid phase.

A technique for simultaneous specific lymphocyte proliferation and IgG production with herpesvirus antigens in solid phase was developed. The cell mediated immune response was highly specific. Stronger cellular responses were found after stimulation with nucleocapsid antigens than with membrane antigens. Varicella-zoster virus (VZV) and herpes simplex virus (HSV) specific antibody production in vitro were found in almost 100% of seropositive individuals, while cytomegalovirus (CMV) antibody production was detectable in 70%. A higher specific IgG production was found after stimulation with CMV and VZV membrane antigens than with CMV nucleocapsid and VZV cell antigens. No differences in IgG production were found with the two types of HSV antigens. A method for viral IgG subclass determination in vitro was also developed. These methods may be used for monitoring immunosuppressed patients for immunological responsiveness to herpesvirus infections.

Antibody Specificity↗
PubMed1985

Nucleoside pools of acyclovir-treated herpes simplex type 1 infected cells.

Nucleoside pools of herpes simplex type 1 (HSV-1)-infected and uninfected African green monkey kidney (GMK) cells and human fetal lung fibroblasts (HL) have been analysed with high-performance liquid chromatography (HPLC). The only nucleosides found in measurable amounts were deoxythymidine (dThd) and adenosine (Ado). The dThd pool seemed to be greater in GMK cells than in HL cells. dThd was also the only nucleoside excreted into the medium. HSV-1 infection reduced the dThd concentration of GMK cells. Addition of acyclovir (ACV) to HSV-1-infected GMK cells inhibited virus replication. This resulted in a dThd concentration similar to that of uninfected GMK cells. dThd added to HSV-1-infected GMK and HL cells reduced the antiviral action of ACV but not that of phosphonoformic acid (PFA). ACV is known to be activated mainly by HSV-induced deoxythymidine kinase (dTK), an enzyme which utilizes dThd as a substrate, while the action of PFA is independent of dTK. The low antiviral activity of ACV in GMK cells as compared to HL cells may be explained by the presence of high amounts of dThd in GMK cells.

Acyclovir↗
PubMed1985

Granulocytopoietic precursor cells and regulatory factors in irradiated human bone marrow.

The effects of irradiation on committed granulopoietic progenitor cells (CFU-C) and granulopoietic humoral regulators were studied in 17 X-ray treated patients with carcinoma of the breast or of the prostate. After 45 or 70 Gy, the CFU-C decreased to 14 +/- 10% in irradiated areas. This remaining CFU-C population probably reflects a combination of radioresistance and survival in situ, and migration of CFU-C from protected marrow areas. The frequency of peripheral blood CFU-C did not change after irradiation. Endogenous colony stimulating activity (CSA), i.e., release of CSA within the marrow cell population, in post-irradiation bone marrow persisted on roughly the same level, indicating a fairly low radiosensitivity of the CSA-producing cells in the bone marrow. Colony stimulating activity in peripheral blood cells and serum remained unchanged, but there were great interindividual variations, and some of the patients with hypercellularity and CFU-C increase in nonirradiated marrow areas also had increased CSA. Serum lipoprotein inhibitors were higher in the post-treatment patients than in healthy control patients.

Bone Marrow↗
PubMed1985

Quantitative analysis of the A, B and H isoantigens in single transitional carcinoma cells.

To obtain objective data on deletion of the ABH isoantigens in bladder carcinoma, microfluorometry was used. Slides were scanned in phase contrast to lessen fading of the immuno- or lectin-fluorescence stained cells. The fluorescence intensity was measured in relation to an external uranyl standard. Staining was most intense in the peripheral and cytoplasmic parts of the cells. The intra specimen fluorescence intensity varied as 1 to 10. In nondeleted cell populations fluorescence intensity means ranged from 1025 to 12,550 and in deleted populations from 304 to 510. Microfluorometry accurately separates deleted cell populations from those with a normal ABH antigen content.

ABO Blood-Group System↗
PubMed1985

Multiplicity dependence and sensitivity of herpes simplex virus isolates to antiviral compounds.

An immunoassay that enables one to assess both viral multiplicity and sensitivity to antiviral drugs, was used to determine the sensitivity of untreated patients' virus isolates. The upper border levels for judging clinical isolates sensitive to Ara-A, ACV, PFA or IDU were calculated from a total of 48 primary herpes simplex isolates. Although five isolates were considered less sensitive to one drug and one isolate to two drugs, all were sensitive at a lower virus multiplicity. Analysis of these isolates showed that no isolate was genetically resistant, but that multiplicity dependence of drugs was high with ACV and Ara-A, lower with PFA. In view of the multiplicity dependence of HSV sensitivity to different drugs, it is recommended that isolates from treatment failures or isolates considered resistant should be assayed in detail.

Acyclovir↗
PubMed1985

Lymphocyte responses after cytomegalovirus infection in bone marrow transplant recipients--a one-year follow-up.

A group of 46 bone marrow transplant (BMT) recipients were studied by lymphocyte stimulation with cytomegalovirus (CMV) antigen before, and repeatedly in the first year after, BMT. Of these, 25 patients developed CMV infection and 68% of these got a positive lymphocyte response to CMV. The recipients with an early response (up to 3 months) to CMV antigen after the CMV infection were less prone to develop chronic graft-versus-host disease (GVHD) than those who responded later or not at all (P = 0.002). After the CMV infection, the increased lymphocyte CMV reactivity remained in recipients without chronic GVHD, but recipients with chronic GVHD usually lost their reactivity. The results suggest that it may be possible to predict patients who are not going to develop chronic GVHD by studying lymphocyte responses to CMV infections.

Antigens, Viral↗
PubMed1985

Activity of the cytomegalovirus genome in the presence of PPi analogs.

PPi analogs and esters of these were studied for their effect on cytomegalovirus (CMV) multiplication. Five aromatic monoesters of phosphonoformate esterified either in the phosphono or the carboxylic group and two diesters were demonstrated to inhibit CMV DNA synthesis and late viral protein synthesis. In a direct assay, the monoesters but not the diesters inhibited CMV DNA polymerase activity. The production of early CMV antigens was not inhibited by any of the compounds. After incubation with either drug for periods up to 7 days, renewed viral production occurred on withdrawal of the compound. All inhibitory esters as well as PPi analogs showed a CMV multiplicity dependence. This was demonstrated both for CMV strain Ad.169 and for all tested CMV isolates. Evidence was found that the esters are hydrolyzed to phosphonoformate and, therefore, may be of importance as useful prodrugs in the specific therapy of CMV infections. The general phenomenon of reversibility to the productive state and the multiplicity dependence of CMV are important factors in any treatment schedule.

Antiviral Agents↗
PubMed1985

Interferon induction in human leukocytes after in vitro exposure to cytomegalovirus or Epstein-Barr virus.

Interferon (IFN) was produced after exposure of human mononuclear leukocytes and bone marrow cells to infectious or noninfectious cytomegalovirus (CMV) in vitro. The IFN was generated mainly by non-B lymphocytes. Both alpha- and gamma-type IFN could be demonstrated. CMV antigens were usually not demonstrable in CMV-exposed leukocytes. Addition of anti-IFN antibodies did not induce CMV antigens. Thus, it seems that the endogenous production of IFN is not responsible for the difficulties in demonstrating CMV antigens after in vitro exposure of normal human leukocytes to CMV. Addition of Epstein-Barr virus (EBV) B95-8 to leukocytes induced the production of alpha-type IFN. Exogenously added IFN reduced the induction of EBV-determined nuclear antigen (EBNA). However, the presence of anti-IFN antibodies in EBV-infected cultures did not increase the number of EBNA-positive cells.

Antibodies↗
PubMed1985

Intravenous foscarnet for the treatment of severe cytomegalovirus infection in allograft recipients.

Foscarnet, trisodium phosphonoformate, was administered intravenously to 6 immunosuppressed patients with life-threatening cytomegalovirus infection. Three of the patients were recipients of a kidney and 3 of a bone-marrow transplant. Favourable clinical responses were seen in 5 of the patients, 2 of whom were still in good health 5 and 8 months after the infection had cleared up. No toxic effect of the drug was detected. The results seem to justify further trials, in which foscarnet should be introduced at an earlier stage of the disease.

Adult↗
PubMed1985

Acyclovir prophylaxis in bone marrow transplant recipients.

Forty-two patients undergoing bone marrow transplantation were included in a randomised, double-blind and placebo controlled trial of prolonged acyclovir prophylaxis against infections with viruses of the herpes group. Twenty patients were allocated to receive acyclovir and 22 to receive placebo. Acyclovir or placebo was administered i.v. at a dose of 250 mg/m2 twice daily, starting 5 days before transplantation. At 5 weeks after transplantation, administration was changed to tablets, 400 mg three times daily (children less than 6 years, 200 mg three times daily) and continued until 6 months after transplantation. In the placebo group, 10 acute herpes simplex virus (HSV) infections occurred in 7 patients (5 HSV-1 and 2 HSV-2), and another patient repeatedly shed HSV in throat washings. Five patients developed herpes zoster. Among patients receiving acyclovir only one episode of HSV infection occurred and no herpes zoster. The difference in the number of infection episodes and the number of infected patients was strongly significant (p = 0.0002 and 0.0017, respectively). The only acyclovir patient who reactivated HSV was terminally ill, and it is highly likely that she did not absorb a sufficient amount of the orally administered drug to control infection. All HSV and varicella zoster virus (VZV) infections were reactivations, and 9 of 10 patients who developed HSV infections or shed virus had a pre-transplantation HSV IgG titer of greater than 10 000 (ELISA). Acyclovir had no effect on cytomegalovirus (CMV), time of engraftment, or graft versus host disease (GVHD). Apart from a possible allergic reaction (skin rash) to acyclovir tablets, no adverse reactions were seen during this long prophylaxis with acyclovir.

Acyclovir↗
PubMed1985

Early results of a trial of the Oka-strain varicella vaccine in children with leukaemia or other malignancies in Sweden.

Nineteen children with acute lymphoblastic leukaemia or other malignancies, aged 3-13 years, with negative histories of varicella-zoster virus (VZV) and of whom 5 were still on regular maintenance chemotherapy, were vaccinated with the Oka-strain varicella vaccine. Mild systemic reactions, involving low-grade fever of a few days duration, were recorded in 4 of the vaccinees. Two of them also developed an extremely sparse rash. A mild local reaction at the vaccination site was observed in 1 child. Conversion rates for circulating VZV antibody, measured at 4-6 weeks and 4-6 months after vaccination using an indirect immunofluorescence test, were 8/12 (67%) and 5/9 (56%), respectively. Markedly lower antibody conversion rates of 5/18 (28%) and 5/14 (36%) were found by means of the enzyme-linked immunosorbent assay method. Corresponding conversion rates for cell-mediated immunity against VZV, determined using a specific lymphocyte stimulation technique, were 9/17 (52%) and 12/14 (86%), respectively.

Adolescent↗
PubMed1984

Eutopic expression of placental-like alkaline phosphatase in testicular tumors.

Very high levels of placental-like alkaline phosphatases (PLAP-like enzymes) were observed in tissues from 13 typical seminomas. Four tumors with seminoma components contained these enzymes to varying degrees, and other testicular tumors had them in smaller or non-detectable amounts. Analysis using monoclonal antibodies produced against the common placental alkaline phosphatase (PLAP) phenotypes and enzyme inhibition studies with amino acids and peptides showed the PLAP-like enzymes present in seminoma to be similar to those PLAP-like enzymes which are expressed in lower amounts in two embryonal carcinomas and in trace amounts in normal testicular tissue. These similarities suggest that the increased expression of PLAP-like enzymes in seminomas results from enhanced eutopic expression of enzymes found in normal testis.

Alkaline Phosphatase↗
PubMed1984

Carcinoembryonic antigen in cytological specimens of urothelial carcinoma.

A peroxidase-antiperoxidase (PAP) technique was developed for the detection of carcinoembryonic antigen (CEA) in urothelial transitional cells of 52 bladder cancer patients. The percentage of CEA-containing malignant cells varied from 10% to 100%. As a mean, 65% of the malignant cells stained for CEA, while the corresponding figure for benign-looking cells was 24%. The results were compared with cytological evaluations, flow cytophotometric results, and immunofluorescent (IF) staining for CEA. With increasing malignancy, more CEA was detected with the PAP technique, whereas the IF technique failed to show this trend. 18 of 20 malignant-tumors had an aneuploid DNA pattern. The two diploid cases were moderately well differentiated. Samples from bladders with heavy inflammation should be avoided in the PAP technique, since the unspecific staining of granulocytes disturbed a correct evaluation of the transitional cells. The PAP technique used on cytological material is recommended for antigen determinations, since good morphology is obtained.

Carcinoembryonic Antigen↗
PubMed1984

Possibilities for an extended classification of bladder cancer.

Patients with bladder cancer were evaluated for T-class, histo-pathological grade and U-CEA (urinary carcinoembryonic antigen) before treatment and the cytological picture 4 months after treatment. Previous work has shown that these variables are not significantly intercorrelated. Scores were computed, consisting of the sums of these (dichotomized) variables. In a statistical analysis with the life-table technique, the scored variables have been log-rank tested for a prognostic trend. In 155 patients, p for symptom-free survival between subgroups with low and high scores was 0.0019 and for relative survival 0.0005. This implies that a combination of variables may have predictive value in bladder cancer.

Actuarial Analysis↗
PubMed1984

Early interactions between human cytomegalovirus and cells.

Adsorption of cytomegalovirus (CMV) to human fibroblasts was not inhibited by preincubation with other herpes viruses (HSV-1, HSV-2, VZV). Transport of virus to the nucleus was studied using virus labelled with 3H-thymidine. Radioactivity was found in the nucleus 20 minutes after virus had been added to the cells. In order to assess the expression of the virus genome, synthesis of early (EA) and late (LA) antigens was studied. Assayed on permissive human lung fibroblasts, a plaque purified virus contained more EA inducing than both EA and LA inducing viral units. Since this was a consistent finding with virions of all densities, it seems to be an effect of viral dose rather than of virion density. Alternatively, LA-defectiveness is a virion property which does not vary with virion density.

Adsorption↗