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Biomedical subjects

B Wahren

Publications and source records attributed to B Wahren.

At least 343 records · Page 19Linked to original sources

Prediction of survival and recurrence in bladder carcinoma.

We have followed a large population of patients receiving radiation treatment for bladder carcinoma with respect to survival and recurrence-free survival. Bivariate and multivariate life table analyses have been performed using a set of independent variables. The most important were T class, grade (G), urinary carcinoembryonic antigen (U-CEA) taken before treatment and cytological analysis 4 months after treatment. We compared the usual way of classifying a patient (T + G) with the combination of U-CEA and cytology since the latter two variables seemed to have great prognostic importance. The analyses show that T + G gives the best significance for survival (p = 0.0003) while U-CEA and cytology is better for recurrence-free survival (rho = 0.0002). 0.0002).

Actuarial Analysis↗

In vitro colony studies in 87 patients with acute nonlymphoblastic leukemia. Prognostic value of colony-stimulating activity and colony-forming cells.

Colony-forming cells (CFU-C) in peripheral blood and bone marrow and colony-stimulating activity (CSA) in mononuclear peripheral white blood cells were studied at diagnosis in 87 patients with acute nonlymphoblastic leukemia (ANLL). Absence of CFU-C in peripheral blood was more frequent in patients who did not enter remission than in those who did, and survival was significantly shorter in CFU-C-negative than in CFU-C-positive patients. No correlation was found between CFU-C in the bone marrow and frequency of remission or survival time. Absence of CSA was significantly more frequent in patients who did not enter remission than in those who did. Only 4 of 28 patients who lacked CSA entered remission. Survival was significantly longer in CSA-positive than in CSA-negative patients. Thus, CSA synthesis in peripheral mononuclear blood cells appears to be a valuable prognostic factor in ANLL.

Acute Disease↗

Influence of cell culture conditions on the inhibition of herpes simplex virus type 1 replication by acyclovir.

Inhibition of herpes simplex virus type 1 (HSV-1) replication, as measured by plaque reduction by acyclovir (ACV), was studied with different cell cultures and under varying conditions. Human lung fibroblasts (HL) required much lower concentrations of ACV for inhibition of virus replication than green monkey kidney (GMK) cells. In both cell types, ACV had to be added within 7 h after infection to cause a full antiviral effect. Pretreatment of cells with ACV before infection did not increase the antiviral activity. ACV caused a stronger inhibition in HL cells which had been confluent for 4 or 7 days as compared with cells just reaching confluence. Addition of ACV and its subsequent removal caused an irreversible plaque reduction in our experiments. ACV gave a pronounced inhibition of thymidine kinase (TK)-positive HSV-1 strains. A relatively small inhibitory effect was seen with a TK-negative HSV-1 strain in HL cells, and no measurable inhibition was seen in GMK cells. Inhibition of HSV-1 replication by ACV was concluded to depend on the type of virus, the cell type used, and the condition of the cells.

Acyclovir↗

Studies of cytomegalovirus infection in renal allograft recipients. II. Serological response to various viral antigens.

In a prospective study the antibody response to various cytomegalovirus (CMV) antigens was examined in 28 renal allograft recipients. Both primary and secondary infections were investigated. Antibodies against immediate early (IEA) and early antigens (EA) were studied by anti-complement immunofluorescence; IgM and IgG antibodies to nuclear late antigens were differentiated by enzyme-linked immunosorbent assay (ELISA). The results of the tests were compared with each other and with those of the complement fixation (CF) test. 5/7 susceptible patients (71%) contracted primary infections. Both IgM and IgG antibodies developed and antibodies to IEA and EA appeared somewhat later. The antibodies to IEA and EA remained detectable throughout the observation period. Secondary infections developed in 20/21 (95%) patients. All initially had CMV antibody levels in ELISA and CF. Rising CMV titers of IgG antibodies were taken as a measure of secondary infection. IgM antibodies developed in only 10/20 (50%) patients. The highest titers of CMV IgM antibody levels were lower in secondary than in primary infections. Antibodies to IEA and EA were present prior to transplantation in some patients, but did not develop in all with secondary infections. The antibody titers were lower just after than before the transplantation in some patients. but subsequently increased again. It thus seems as if the humoral immune response to these CMV antigens differs in primary and secondary infections.

Adult↗

Development of sensitive and enzyme-linked immunoassays for herpesvirus antigens and some applications.

Sensitive enzyme-linked immunoassays for herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) were developed. Both a sandwich technique, using antiviral antibodies from two species to detect the antigen, and an inhibition assay where the sample antigen was incubated with one antiserum, could be used. Around 4-50 ng of viral antigens (measured as protein content) could be detected. The ELISA inhibition technique using type-specific antisera could differentiate between HSV-1 and HSV-2 strains. These could also be distinguished in clinical samples. For CMV, both early and late antigens could be measured as well as the antigenic activity of CMV DNA polymerases. CMV activity in clinical specimens could be detected. The inhibition technique for VZV antigen determination appeared suitable for direct typing of clinical material. No cross-reaction with HSV was seen.

Animals↗

Viral antibody activity of oligoclonal and polyclonal immunoglobulins synthesized within the central nervous system in multiple sclerosis.

Thin-layer polyacrylamide gel isoelectric focusing (PAG IEF), a very high capacity method for separating immunoglobulins (Ig), was performed on cerebrospinal fluid (CSF) and serum. It was followed by antigen immunofixation with measles, mumps, herpes simplex (HSV), and rubella virus antigens and anti-human Ig autoradiography in order to demonstrate viral antibodies in separated Ig zones. Two of 11 control patients and 21 of 25 patients with multiple sclerosis (MS) displayed one or more zones of viral antibodies in the CSF without any counterpart, or with distinctly fainter zones, in the serum. Such reaction patterns were taken to indicate the possibility of intrathecal antibody synthesis. Antibody synthesis to measles was found in one to five zones in 76% of the patients with MS; antibody zones were found to HSV in 36% of the patients, to mumps in 12%, and to rubella in 12%. In 36% of the patients, two or three different antibody specificities (of which one was always measles) were found simultaneously in individual autoradiogram zones. For all viral antibodies detected in the CSF autoradiograms, their counterparts in oligoclonal or polyclonal IgG zones (or both) were demonstrable by PAG IEF of the corresponding CSF. The majority of patients with MS also had one or more oligoclonal CSF IgG zones without known antibody specificity. Antigen immunofixation and autoradiography are mainly qualitative. It is not known whether the viral antibodies present in oligoclonal or polyclonal IgG zones in MS CSF reflect a polyclonal B cell activation, a disease-specific immune reaction, or both.

Adolescent↗

Antibody response to cytomegalovirus: a comparison between adult patients with neurological disease and uncomplicated infection.

Cytomegalovirus (CMV) infection in adults can cause neurological diseases such as the Guillain--Barré syndrome (GBS) and myelitis. The mechanism leading to the development of neurological damage is, however, still unknown. We have investigated the possibility that an abnormal humoral immune response, either weak or hyperactive, could be the cause. The antibody response of four patients with a primary CMV followed by neurological symptoms was compared to that of four age-matched controls with an uncomplicated infection. IgG and IgM antibodies to CMV early antigens (EA), late antigens (LA), and IgG antibodies to CMV immediate early antigens (IEA) were measured in consecutive serum samples. Comparison of titers indicated a longer time lapse between the onset of CMV infection and the development of symptoms in the group with neurological disease. We found no conclusive evidence of an abnormal humoral immune response to CMV in the patients with neurological disease compared to the patients with an uncomplicated infection.

Adolescent↗

An interchangeable ELISA for cytomegalovirus antigen and antibody.

An enzyme-linked immunosorbent assay (ELISA) was developed to demonstrate cytomegalovirus (CMV) antibodies and antigen. A nuclear antigen from CMV-infected cells was used for detection of IgG and IgM antibodies. Significant rises of CMV-IgG and significant levels of CMV-IgM were found in sera from patients with acute CMV only, and not with other herpesvirus infections. CMV antigens were demonstrated in cells and in culture medium by a sandwich or by an inhibition ELISA technique. In the sandwich technique, the plates were coated with monkey anti-CMV IgG and rabbit anti-CMV IgG was used as the second antibody. Both early and late CMV antigens were identified with this method. Treatment of CMV containing samples using freeze--thawing or detergent reduced the infectivity, but the antigenicity was not affected. There was no cross-reactivity with herpes simplex or varicella-zoster virus.

Antibodies, Viral↗

Conditions for cytomegalovirus stimulation of lymphocytes.

Lymphocytes from healthy donors or from patients with chronic lymphocytic leukaemia were subjected to live or inactivated cytomegalovirus (CMV) or the mitogen phytohaemagglutinin. No early or late CMV antigens could be demonstrated in the lymphocytes, indicating that neither abortive nor replicative CMV infection takes place. Only cells from CMV antibody-positive leukaemic and non-leukaemic donors were stimulated by CMV to DNA synthesis, with a maximum on day 5. Cells from all individuals responded to phytohaemagglutinin stimulation, the peak of activity occurring on day 3. The stimulation with CMV occurred in T cells and was independent of early CMV antigen production, viral DNA synthesis, or viral replication. CMV is thus not an in vitro lymphocyte mitogen like Epstein-Barr virus but is a very potent antigen for memory T cells.

Antibodies, Viral↗

Serum level of biliary glycoprotein I, a determinant of cholestasis, of similar use as gamma-glutamyltranspeptidase.

Biliary glycoprotein I (BGP I), a constituent of normal bile and serum, is a glycoprotein (mol. wt. approximately 90,000) containing about 40% carbohydrate. Serum BGP I (S-BGP I) was determined by means of a double-antibody radioimmunoassay in patients with liver and gastrointestinal disease and in healthy individuals. The serum levels of five liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (S-ALP), gamma-glutamyltranspeptidase (S-GT), and lactic dehydrogenase), bilirubin (total and conjugated), and bile acids (cholic and chenodeoxycholic acid) were determined in parallel. Healthy individuals had 0.5 +/- 0.3 mg/l of S-BGP I (mean +/- 2 S.D.; range, 0.2-0.9 mg/l). Most patients with liver disease (chronic hepatitis, alcoholic cirrhosis, primary biliary cirrhosis) had elevated levels, up to 5-10 times the upper reference limit, whereas most patients with gastrointestinal disease (ulcerative colitis, Crohn's disease, other GI diseases) had normal values. In patients with liver disease S-BGP I was positively correlated (p less than 0.0005) to S-GT. In primary biliary cirrhosis a positive correlation (p less than 0.005) between S-BGP I and S-ALP was also obtained. All other comparisons between S-BGP I and the other liver function tests showed non-significant correlations. It is concluded that S-BGP I is a determinant of cholestasis of similar use as S-GT.

Adolescent↗

Assessment of serial CEA determinations in urine of patients with bladder carcinoma.

Carcinoembryonic antigen (CEA) levels in urine and serum from 294 patients with bladder cancer in varying stages have been clinically evaluated. All urine samples were obtained from patients with intact renal function and without bacterial infection in the bladder. The samples were collected before, during, and at follow-up examination after radiotherapy. They were perchloric acid extracted before being assayed in a double-antibody radioimmunoassay. The geometric mean of urine CEA levels for patients with primary tumors of Stage T1 or T2 was significantly lower than that for those with Stage T3 or T4 disease. The urine CEA levels for patients with tumors of various histologic grades did not differ. The urine CEA levels decreased from before to after radiation treatment of the primary tumor. Patients with recurrence within six months after undergoing primary treatment had higher initial mean urine CEA levels than did those without evidence of recurrence. The prognostic information for recurrence was limited to the more advanced tumors. Differences were also found between the means of samples taken before recurrence and after treatment of recurrent tumors; with regression of the tumor, a lower mean urine CEA level was found; with progression, a higher value. Urine CEA levels before any treatment were higher when the patients had a short survival time. Serum CEA levels were not related to stage or grade of the primary bladder tumor but levels were slightly elevated with metastases. The determination of urine CEA levels seems to be useful in the follow-up of patients with bladder carcinoma because when initially high, it adds to the information of the T classification and predicts early recurrence, and the monitoring of individual patients after primary treatment is useful for detecting recurrence.

Aged↗

Distribution of tumor-associated antigen CEA and cross-reacting NCA in fetal organs.

The organ distribution of the tumor-associated carcinoembryonic antigen (CEA), and that of the normal tissue component NCA (non-specific cross-reacting antigen) have been investigated in the fetus. Organ extracts from five fetuses between 14 and 21 weeks of age were analysed by radioimmunoassay using specific antisera. CEA was detected in large amounts (800--1,650 ng/g) in fetal colon and in barely detectable amounts in lung and placental tissue. This differed from NCA, which could be detected in almost all organ extracts analysed. The highest concentration of NCA was measured in fetal colon and the content increased with the gestational age of the fetus. High amounts of NCA were also found in the liver, spleen and placental tissue. The gel elution profiles of CEA and NCA from an amniotic fluid pool and a pool of colonic extracts were also determined. CEA eluted similarly to the marker 125I--CEA purified from liver metastasis of colonic carcinoma. The NCA-reactive material was found in three distinct peaks.

Amniotic Fluid↗

Inhibition of cytomegalovirus late antigens by phosphonoformate.

Phosphonoformate (PFA) at a concentration of 500 muM and higher completely inhibited the replication of cytomegalovirus (CMV) in cell culture. 50% inhibition was obtained at a concentration of muM PFA. Early nuclear CMV antigens appeared uninhibited, but the formation of nuclear inclusion bodies, late cytoplasmic antigens, Fc-receptors and CPE were all inhibited by PFA. No visible cell toxicity was noted at the PFA concentrations and exposure times used.

Antigens, Viral↗

Reversible inhibition of cytomegalovirus replication by phosphonoformate.

Cytomegalovirus (CMV Ad. 169)-induced late antigens are specifically inhibited by phosphonoformate (PFA). Four fresh isolates of CMV were also inhibited by PFA to varying degrees. The kinetics of CMV immediate early antigens (IEA) and early nuclear antigens (EA) produced in the presence of PFA were compared to the early phase of the replicative infection. After anticomplement immunofluorescence with anti-IEA and anti-EA, microimmunofluorometry of individual CMV-infected nuclei was performed. CMV-induced antigens had a two-wave appearance, with maxima at 6 and 24 h postinfection. The same was seen in the presence of PFA. CMV EA-containing cells persisted for more than 5 weeks in the presence of PFA, but decreased in frequency and antigen content. The inhibition of virus replication was reversible after all incubation periods assayed. After PFA release, IEA and EA appeared again in many cells, and the kinetics were similar to that of initial infection. The results suggest that the input CMV genome persists in most initially infected cells, survives PFA incubation, and is active again after PFA release. This differs from abortive CMV infections.

Animals↗

Influence of cells and virus multiplicity on the inhibition of herpesviruses with acycloguanosine.

The inhibition of herpes simplex virus type 1 (HSV-1) plaque formation by acycloguanosine (ACG) was assayed in human fetal lung fibroblasts (HL), cell lines from human cervical carcinoma, rabbit cornea, and human rhabdomyosarcoma, and three green monkey kidney cell lines. The ACG concentration giving 50% plaque reduction (PR50) of HSV-1 was lowest in HL. In two green monkey kidney cell lines, HSV-1 plaque formation was relatively insensitive to ACG, with PR50 of 25 and 60 muM, respectively. In the other cells, HSV-1 showed an intermediate sensitivity to ACG. Also, HSV-2 was more sensitive to ACG in HL than in monkey kidney cells. HSV-1 plaque reduction on HL cells was studied as a function of increasing virus MOI with a constant concentration of ACG. An increased MOI decreased the sensitivity to ACG. The sensitivity of cytomegalovirus (CMV), strain Ad. 169, and four fresh CMV isolates to ACG was studied in HL cells. At low MOIs, three of the five CMV strains were somewhat sensitive to ACG, PR50 values ranging from 60 to 450 muM ACG. At high MOIs none of the virus strains were sensitive. ACG at concentrations of 200 muM or less did not significantly affect host cell DNA synthesis, as measured by 3H-thymidine incorporation. In cell culture, the inhibition of herpesviruses by ACG appears to be complex, depending on the type of virus, virus concentration, type of host cells, and condition of the cells.

Acyclovir↗

Placental alkaline phosphatase, alphafetoprotein and carcinoembryonic antigen in testicular tumors. Tissue typing by means of cytologic smears.

Indirect immunofluorescence and radioimmunoassay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcinoembryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells. Embryonal carcinomas had AFP- and CEA-containing cells, sometimes PLAP. PLAP and sometimes CEA were found in seminoma cells. Sera from patients with advanced non-seminomatous tumors could contain any of these antigens or any combination of them. Sera from patients with seminomas had raised PLAP or CEA. PLAP appears to be a new marker for seminoma.

Adolescent↗