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Biomedical subjects

B Wahren

Publications and source records attributed to B Wahren.

At least 325 records · Page 18Linked to original sources

Tumour and cellular localization by use of monoclonal and polyclonal antibodies to placental alkaline phosphatase.

Monoclonal and polyclonal antibodies against placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hep 2 tumours in nude mice. The antibodies were labelled with 125I and injected i.p. in mice with developing Hep 2 tumours. The distribution of 125I-anti PLAP in various tissues showed that the labelled antibody was enriched in the tumour, the mean concentration ratio being 7.1 and 6.8 for polyclonal and monoclonal antibodies, respectively. A PLAP negative tumour (RD) showed a mean ratio of 1.2. There was a positive correlation between PLAP content and uptake of labelled antibody in the tumours. Hep 2 tumour cells in tissue culture showed 100% positivity for PLAP, while imprints of the tumour after passage in nude mice showed 40-50% positivity. PLAP offers potential as a useful marker for localizing tumours in humans.

Alkaline Phosphatase↗

Transfer and persistence of viral antibody-producing cells in bone marrow transplantation.

Antiviral humoral reactivity was studied after bone marrow transplantation. Antiviral IgG--reflecting the presence of functional B cells--was found for a substantial period after transplantation. However, most patients unexpectedly stopped producing antibody after an extended period of observation (i.e., for more than three months and up to as long as 12 months). This cessation was noted whether the viral reactivity involved was of donor or recipient origin. The transferred viral antibody-producing cells thus usually persisted for only a moderate length of time and seemed to have a finite life span. The findings indicate that donor and recipient memory cells are susceptible to the conditioning regimen or to the treatment that follows transplantation. In a few cases transferred immunity of long duration was seen; this finding indicated the occasional engraftment of memory cells.

Antibodies, Viral↗

Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease.

Of 68 consecutive allogeneic bone marrow transplant patients, 53 survived more than three months after transplantation. Twenty-two (42%) developed chronic graft-versus-host disease (GVHD). Chronic GVHD was more common among patients who had previously experienced cytomegalovirus (CMV) infection (20/36, 56%) than among those without signs of active CMV infection (2/17, 12%) (P less than 0.01). The CMV infections preceded the development of chronic GVHD by a median of 128 days (range 23-322 days). Children below 14 years of age who had had CMV infection developed chronic GVHD as often as older patients (8/14 vs. 12/22). CMV infection may pave the way for chronic GVHD.

Adolescent↗

IgG-subclass-specific CMV reactivity in bone marrow transplant recipients.

IgG subclasses of cytomegalovirus (CMV) antiviral antibodies were determined in 37 donor-recipient pairs of bone marrow transplants (BMT). Bone marrow transplant recipients, like healthy persons, have a restricted immune reactivity, producing mainly two types of anti-CMV IgG: IgG1 and IgG3. Passively transfused specific antibody subclasses were readily measurable. Take of the transplant could be detected from the production of subclass IgG antiviral antibody 1-3 months after BMT of seronegative recipients with marrow from seropositive donors. Patients with protracted CMV infections or other severe diseases initially also produced CMV IgG1 and IgG3, but anti-CMV subclass titers then decreased. In severe disease, CMV was isolated from blood cells as well as from urine. In moderate infections, in which the patients recovered, CMV was isolated from urine but usually not from blood, and a strong and durable antiviral subclass response was measured.

Anemia, Aplastic↗

Virus-specific immunoglobulin G subclasses in herpes simplex and varicella-zoster virus infections.

The subclass specificities of antiviral immunoglobulin G (IgG) produced in response to herpes simplex and varicella-zoster virus infections were investigated. IgG1 and IgG3 with anti-herpes simplex virus activity were seen in patients with primary and reactivated disease, as well as in healthy seropositive subjects and in immunoglobulin preparations. IgG4 was occasionally seen alone or together with IgG1 and IgG3 in patients. In varicella, IgG3-specific antiviral antibodies were predominant, whereas in zoster, IgG1 was the dominant subclass.

Antibodies, Monoclonal↗

A novel method for determining the sensitivity of herpes simplex virus to antiviral compounds.

A rapid and sensitive assay was developed to analyse the sensitivity of wild type HSV-1 and HSV-2 isolates with respect to a battery of antiviral substances. In the viral sensitivity assay, human embryonic lung fibroblasts are incubated with the virus isolate and different concentrations of the antivirals. After 1-3 days, the cells are disrupted and analysed for HSV type 1 or 2 antigens by an enzyme-linked immunosorbent assay. Antigens corresponding to 17 plaque-forming units were detectable after 1 day of incubation. After 3 days, HSV antigens derived from less than one plaque-forming unit were measurable. The sensitivities of 22 HSV-1 and 19 HSV-2 primary isolates from untreated patients were tested against adenosine arabinoside, acyclovir, phosphonoformic acid and iododeoxyuridine. Each isolate was found to have an individual pattern of sensitivities to the different antivirals. Five isolates were judged to be relatively resistant to one or more of the drugs tested.

Antigens, Viral↗

Computer-based virus sensitivity assay and neutralization method. Applications for herpesviruses.

A method for computerized analysis of the antiviral efficiency of drugs and immunoglobulins was developed. The sensitivities of herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) to antiviral drugs were determined. A new type of neutralization assay could be performed rapidly and accurately with HSV and CMV. Combining immunological methods for herpesvirus antigen detection with a computerized analysis permitted rapid, sensitive measurement of drug sensitivities, comparison of antiviral activities at various virus concentrations and selection of potent neutralizing antisera.

Antibodies, Viral↗

A clinical evaluation of serum placental alkaline phosphatase in seminoma patients.

Serum levels of placental alkaline phosphatase (PLAP) were measured in 100 patients with seminoma. A specific double antibody radioimmunoassay was used. PLAP was elevated for 9 out of 21 patients with primary tumours, to a mean of 53 micrograms/l. Of the 12 cases with recurrent or metastatic growth, nine had raised PLAP. The sensitivity of PLAP determinations for primary and advanced disease was 55%. After successful treatment of seminoma, the PLAP level decreased. In a group of 68 patients with no evidence of disease, nine had slightly elevated serum PLAP. In many, but not all patients, serum PLAP parallelled the changes in tumour burden. In such patients and for follow-up of treatment, PLAP might be used as a new marker for seminomatous disease.

Adult↗

Decrease of a normal colon and granulocyte antigen (NCA) in whole lysed blood of myelosuppressed patients.

A normal colon and granulocyte antigen (NCA) is found in large amounts in neutrophil granulocytes. A method combining freeze-thawing and ultrasonication of whole blood proved to be the most efficient in recovery of NCA from separated granulocytes or whole blood. NCA in whole blood was studied in healthy persons and in 8 patients with embryonal carcinoma undergoing chemotherapy, with a myelosuppressive effect. A strong correlation (r = 0.96) between the total number of peripheral granulocytes and the amount of NCA in lysed whole blood was found in both healthy persons and myelosuppressed patients. The NCA content per 10(9) granulocytes was equal in granulocytopenic and healthy persons. NCA measurements therefore give information about the total number of granulocytes in peripheral blood within the limits measured (0.5-6.5 x 10(9) granulocytes/l).

Agranulocytosis↗

NCA: a differentiation antigen of myelopoietic cells in humans and hominoid monkeys.

NCA, a normal colonic and granulocytic antigen, could be demonstrated in serum and in myelopoietic, but not lymphopoietic or erythropoietic, cells of Homo sapiens and other Primates. The levels of NCA in both serum and myelopoietic cells of Homo and hominoids were higher than those of more distant relatives of the same order. Thus, the classic phylogenetic differences are reflected also by the distribution of NCA. Hyperimmunization of Macaca irus, in which the NCA content of serum and cells is low, led to occurrence of anti-NCA IgG in all animals. The phylogenetic differences may accordingly have to do with slight antigenic NCA differences between Homo and other Primates rather than differences in amount only. Purified NCA did not affect growth and maturation of myelopoietic stem cells in vitro, whereas anti-NCA inhibited development of the majority of myelopoietic clusters and colonies.

Animals↗

Virus-specific antibody activity of different subclasses of immunoglobulins G and A in cytomegalovirus infections.

Healthy donors and patients with primary or reactivated cytomegalovirus infections were examined for antiviral antibodies of the immunoglobulin G (IgG) and IgA subclasses. For this purpose, monoclonal antibodies against the four IgG and the two IgA subclasses were used in enzyme-linked immunosorbent assays with cytomegalovirus antigen. IgG1 and IgG3 were the principal anti-cytomegalovirus subclasses in serum samples from healthy donors and patients. IgG1 was higher in reactivated than in primary disease. Cytomegalovirus-specific IgG2 was detected only in serum samples with high total cytomegalovirus IgG. A few patients with high total serum IgG4 also had cytomegalovirus-specific IgG4 antibodies. During convalescence, there was no significant increase in total IgG of any subclass. Both IgA1 and IgA2 antibodies with cytomegalovirus specificity were detected in patients who had cytomegalovirus antibodies of the IgA class.

Antibodies, Viral↗

Tumor localization of CEA-containing human tumors in nude mice by means of monoclonal anti-CEA antibodies.

Three different monoclonal antibodies (mabs) directed against conformation-dependent protein determinants in carcinoembryonic antigen (CEA) were evaluated for tumorimmunolocalization of CEA-containing human tumors grown in nude mice. The antibodies were of high affinity and of the IgG1 subclass. They did not react with non-specific cross-reacting antigen (NCA), biliary glycoprotein I (BGP I) or orosomucoid. 10-20 muCi (1-2 micrograms) of 131I-labelled mab was injected intraperitoneally into mice bearing heterografts of the CEA-containing human tumor cell lines LS 174T, Detroit 562 or HT-29 or into mice bearing grafts of the non-CEA-containing human tumor cell line RD. The concentration of radiolabelled mab in the tumor compared with the mean concentration in the mouse increased up to day 4 after injection. In contrast, the concentration ratios of radioactivity in the other tissues decreased with time. Excellent tumor localization was obtained with mab 38S1 in mice bearing LS 174T tumors. The concentration of radioactivity (cpm/g) tissue wet weight) was 24-390 times higher in the tumor than in the muscle. The difference between tumor and liver and between tumor and blood was 4-89 times and 2-25 times, respectively. A mean value of 40% of the total radioactivity in the mouse at day 4 was localized to the tumor. Mab 38S1 also showed positive tumor localization in mice carrying Detroit and HT-29 tumors. Means of 22% and 18% of the total radioactivity in the mouse at day 4 were found in these tumors, respectively. Mab 38S1 was, however, not enriched in the tumor of mice bearing the non-CEA-containing sarcoma RD. Furthermore, when LS 174T tumor-bearing mice were injected with normal mouse IgG, no enrichment of radioactivity in the tumor was seen. Positive tumor localization with mab 48 was obtained while mab 9 was not enriched in the tumor. Scanning pictures of LS 174T-grafted mice on day 4 after injection of 131I-mab 38S1 showed a definite radioactive spot corresponding to the tumor and in addition a spot corresponding to the liver or the heart.

Animals↗

Urinary CEA for prediction of survival time and recurrence in bladder cancer.

The prognostic information from carcinoembryonic antigen was evaluated in bacteria-free urines of patients with bladder carcinoma. Patients with elevated (greater than or equal to 30 ng/ml) U-CEA had a poorer relative and symptom-free survival than patients with initial U-CEA below 30 ng/ml. Patients in whom U-CEA decreased from before to after radiation treatment had a better survival rate than patients with increasing U-CEA. These findings were most significant in cases with large (T3 + T4) tumors or with tumors of a lower differentiation (G3). U-CEA appeared to be an independent variable for prognostic evaluation of survival, since these differences were also true within the subgroups of known variables such as classes or grades. All but one of the patients, in whom short-term local control was obtained, had a posttreatment U-CEA below 50 ng/ml. In oncology units, where the more malignant bladder tumors are treated, U-CEA determinations may indicate which patients require intensified monitoring or treatment.

Adult↗

Pyrophosphate analogues as inhibitors of DNA polymerases of cytomegalovirus, herpes simplex virus and cellular origin.

Several pyrophosphate analogues have been compared for their ability to inhibit the activities of isolated cytomegalovirus (CMV) DNA polymerase, herpes simplex virus type 1 (HSV 1) DNA polymerase and calf thymus DNA polymerase alpha. The most effective inhibitors were phosphonoformate and phosphonoacetate. Although not identical, the structural requirements for compounds inhibitory to CMV and HSV-1 DNA polymerase were specific, with two negatively charged groups in close vicinity. The CMV DNA polymerase was more susceptible to certain phosphonoacetates containing bulky hydrophobic alpha-substituents than was the HSV-1 DNA polymerase. No example of the converse preference was found. The inhibition of CMV DNA polymerase by phosphonoformate, hypophosphate, alpha-hydroxyphosphonoacetate and alpha-nonylphosphonoacetate was linear non-competitive with the deoxyribonucleoside triphosphates as variable substrates. Phosphonoformate, phosphonoacetate, and to a lesser extent alpha-hydroxyphosphonoacetate, carbonyldiphosphonate and alpha-nonylphosphonoacetate also inhibited the focus formation by CMV in cell-culture.

Animals↗

Clinical evaluation of NCA in patients with chronic myelocytic leukemia.

NCA, a normal colon and granulocyte antigen, which has been found in large amounts in myelocytes and metamyelocytes and in smaller amounts in neutrophil granulocytes, was studied in 50 CML patients in various stages of the disease. Radioimmunoassay was used to demonstrate NCA in serum. Untreated CML patients had a mean level of 732 micrograms NCA/l, poorly controlled patients 421 micrograms/l and well-controlled patients 160 mu/l. These values differ significantly from the mean of healthy persons, which was 71 micrograms NCA/l. The serum NCA levels were related to the number of maturing myeloid cells in blood, and to the clinical course in the chronic phase of CML. In blast crisis low values with a mean of 109 micrograms NCA/l was found. Patients with ANLL had a low mean level, 50 micrograms/l. Low levels of NCA could not be attributed to antibodies to NCA. NCA is a normal myeloid differentiation antigen. Despite this, its occurrence in serum in leukemic patients differs from normal. This probably has to do with the abnormal amount as well as the release of NCA by leukemic maturing myeloid cells.

Antibodies↗

Adsorption of purified human cytomegalovirus and induction of early antigens in different cells.

Different human and nonhuman cells were assayed for their capacity to absorb human cytomegalovirus (CMV Ad.169) and to support CMV infection in vitro. The CMV adsorptive capacity was assayed by measuring cell-bound radioactivity after addition of purified 3H- or 125I-labeled CMV or by a bioassay for residual infectious virus in the supernatant fluid. Many of the human and nonhuman cell types adsorbed CMV. Induction of CMV early nuclear antigens in the same cells was assayed by anticomplement immunofluorescence staining of fixed cells 1-3 days after infection. CMV early antigens were induced in the human and nonhuman cells that showed a high degree of CMV adsorption.

Adsorption↗