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Biomedical subjects

B Wahren

Publications and source records attributed to B Wahren.

At least 289 records · Page 16Linked to original sources

Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infection.

The first 72 consecutive bone-marrow transplant recipients with haematological malignancies (29 with acute nonlymphoblastic leukaemia, 31 with acute lymphoblastic leukaemia, nine with CML and three with myelofibrosis, IgA myeloma and T-cell lymphoma, respectively) were investigated for the frequency of relapses 1 year or later after bone-marrow transplantation. Seven relapses occurred from 30 to 850 d after transplantation (median 180 d). All relapses occurred in patients with acute leukaemia less than or equal to 18 years of age with a high risk for relapse, i.e. transplanted in second or later remission or with more than 10% blasts in the marrow before transplantation. Among all patients the probability of relapse was increased in patients without cytomegalovirus (CMV) infection (P = 0.001) and in patients without chronic GVHD (P = 0.049). Among leukaemic patients less than or equal to 18 years of age with a high risk of relapse all relapses occurred in patients (n = 11) without CMV infection, whereas no relapses were seen in patients (n = 13) with CMV infection (P = 0.006). Known risk factors for leukaemic relapse were comparable in both groups.

Acute Disease↗

Induction of immunoglobulin secretion and DNA synthesis in human lymphocytes in vitro by cytomegalovirus preparations.

Immunoglobulin secretion as evidenced by plaque-forming cells (PFC) in an indirect haemolysis-in-gel assay, and DNA synthesis were induced in human blood lymphocytes by the following preparations of cytomegalovirus (CMV): Nucleocapside Nc-CMV antigen, membrane M-CMV antigen, crude C-CMV preparations and CMV-incubated adherent cells. Peak stimulations occurred around day 6 in culture. Nc-CMV and M-CMV only stimulated PFC and DNA synthesis in lymphocytes from CMV seropositive individuals. C-CMV also stimulated lymphocytes from CMV seronegative individuals but gave better responses in lymphocytes from CMV seropositive individuals. CMV-incubated adherent cells occasionally stimulated lymphocytes from CMV seronegative individuals but always in CMV seropositive blood donors. Nc-, M-, and C-CMV gave high numbers of PFC in B cells enriched by sheep erythrocyte sedimentation and in co-cultures of enriched T and B cells. Almost no PFC were induced in enriched T cells. DNA synthesis induced by all the three antigenic CMV preparations increased after removal of adherent cells. Strong DNA synthesis was induced in enriched T cells compared to almost none in enriched B cells. It is concluded that some pure CMV preparations act as antigens and more crude preparations induce polyclonal activation. Different CMV preparations may be used to diagnose CMV, to study immune reactivity against CMV and as a model for CMV infections in vitro.

Antibody Formation↗

Comparative methods for detection of thymidine kinase-deficient herpes simplex virus type 1 strains.

Four methods for analyzing viral susceptibility to antiviral substances were compared. In two methods viral products were measured: late viral proteins were measured by an enzyme-linked immunosorbent assay and viral DNA was measured by DNA hybridization. Infectious virus was quantified in the other two assays as the number of plaques and the yield of virus. The enzyme-linked immunosorbent assay procedure in our hands detected the smallest amounts (lowest proportions) of thymidine kinase-deficient herpes simplex virus type 1 mixed with wild-type virus. The thymidine kinase-deficient proportion of the herpes simplex virus type 1 isolate increased rapidly in the presence of acyclovir in cell culture.

Acyclovir↗

Enhancive and suppressive effects of cytomegalovirus on human lymphocyte responses in vitro.

Virus-specific lymphocyte proliferation in the presence of cytomegalovirus (CMV) without and with monocytes was studied in healthy persons. Three categories of lymphocyte response could be distinguished: seropositive low responders, naturally high responders, and lymphocyte populations responding well to CMV antigen in the presence of added CMV-incubated autologous monocytes. This latter category could be identified by preincubating autologous monocytes with CMV. CMV-seronegative persons were nonresponders. Early CMV antigens were produced in monocytes but not in lymphocytes by all CMV isolates. Infection of monocytes as detected by antibody to early viral protein did not appear to abort the antigen-presenting ability. The virus-specific responding lymphocytes were mainly of the T4+ phenotype. In contrast, addition of CMV to polyclonal mitogens significantly suppressed total lymphocyte DNA synthesis. CMV thus may have an enhanced virus-specific stimulatory effect on lymphocytes together with monocytes but a suppressive effect on the total lymphocyte population.

Autoradiography↗

The importance of pre bone marrow transplantation serology in determining subsequent cytomegalovirus infection. An analysis of risk factors.

The yearly incidence of cytomegalovirus (CMV) infection among 73 consecutive bone marrow transplant (BMT) recipients was 68%. Recipients with negative CMV serology prior to transplantation had a yearly incidence of CMV infection of 35% compared to 87% in CMV seropositive patients (p = 0.0001). When the ages of donors and recipients were analysed as continuous variables, both recipients with a younger donor and young recipients had a lower incidence of CMV infection (p = 0.04; p = 0.05). White cell transfusions were significantly associated with an increased incidence of CMV infection (p = 0.03). If white cell transfusions were controlled for, lower marrow cell doses were significantly associated with an increased risk of CMV infection, compared to higher cell doses (p = 0.035). In multivariate analyses, the impact of negative recipient serology was so strong that the other analysed factors did not affect the prognosis for CMV infection, when taken together or separately. 14 patients had symptomatic CMV infection and 13 of those were seropositive prior to BMT. The one-year incidence of symptomatic CMV infection was 33%. None of 12 clinical factors analysed were significantly associated with symptomatic CMV infection. The CMV antibody titer level prior to BMT was not correlated to the risk for symptomatic CMV infection and/or death. The ability to respond with a significant titer rise after BMT was lowered for patients with interstitial pneumonitis compared to patients with other clinical symptoms of CMV infection.

Adolescent↗

Long-term acyclovir prophylaxis in bone marrow transplant recipients and lymphocyte proliferation responses to herpes virus antigens in vitro.

In this randomized double-blind and placebo controlled trial of 6 months' prophylaxis with acyclovir (ACV) in 42 bone marrow transplant (BMT) recipients, patients receiving ACV had fewer herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections during the prophylaxis compared to the placebo treated patients (P less than 0.05). During the first 6 months after the prophylaxis had been discontinued the frequency of clinical HSV reactivations was low both in the ACV (1/13) and in the placebo (1/13) treated patient groups. Altogether the ACV treated patients had significantly fewer HSV reactivations during the first year after BMT (P less than 0.05). The HSV-specific lymphocyte proliferation response was also lower in the ACV treated group at 3, 6 and 12 months after BMT (P less than 0.05). VZV infections recurred rather frequently, however, after discontinuation of ACV prophylaxis. Therefore no difference was found in the number of VZV infections during the first year after BMT. The VZV-specific lymphocyte proliferation response was significantly lower in the ACV treated group only at 6 months (P less than 0.05). ACV prophylaxis had no effect on the frequency of CMV infections; CMV-specific lymphocyte proliferative responses were not decreased.

Actuarial Analysis↗

Sensitivity of cytomegalovirus to intravenous foscarnet treatment.

Intravenous foscarnet was given on an emergency basis to 30 immunosuppressed patients with cytomegalovirus (CMV) disease, of whom 28 were organ transplant recipients. Thirteen patients responded to foscarnet by cessation of CMV secretion. The in vitro sensitivity to foscarnet of the CMV isolates from non-responders before, during and after foscarnet treatment was similar to that of viral isolates from responders before or during foscarnet treatment and also to CMV isolates from non-treated patients, with mean in vitro IC50 values of 239-294 microM of foscarnet. Thus, there was no evidence of increased resistance of the CMV isolates obtained after foscarnet treatment. A higher total foscarnet dose appeared to favor response.

Antiviral Agents↗

Cytomegalovirus-specific lymphocyte proliferation and in vitro cytomegalovirus IgG synthesis for diagnosis of cytomegalovirus infections after bone marrow transplantation.

With new techniques 19 bone marrow transplant (BMT) recipients were monitored for lymphocyte proliferation and specific IgG production in vitro by cytomegalovirus (CMV) antigen in solid phase. Twelve patients got a reactivated CMV infection as defined by virus isolation or serum IgG conversion. Lymphocyte proliferation and in vitro IgG production responses were significantly stronger in these 12 patients than in seven without ongoing CMV infection (P = .02). CMV infection was indicated by the lymphocyte responses at a mean of 45 days after BMT as against a mean of 79 days that passed before CMV growth in culture was detected (P less than .05). Lymphocyte proliferation and in vitro IgG production may thus be used as tools for diagnosis and for monitoring of CMV infections in BMT recipients.

Adolescent↗

Polyclonal and monoclonal anti-CEA antibodies in immunolocalization of colorectal cancer.

Antibodies to carcinoembryonic antigen (CEA) from sheep and monkey were immunoadsorbent purified. Mouse monoclonal antibody (MAb) anti-CEA I-38S1 and Fab fragments of this antibody were prepared from mouse ascitic fluid. The IgG preparations were labelled with 123I or 131I, the Fab fragments with 131I. The antibody reactivity was unchanged after labelling. Patients with advanced colorectal carcinomas received an intravenous injection of 50-200 MBq 123I or 30-160 MBq 131I coupled to 250-500 micrograms antibody or antibody fragment. Patient examinations were performed using emission tomography (SPECT) and/or conventional gamma camera scintigraphy. The specific localization of labelled anti-CEA to tumor was compared to known tumor localized by CAT-scan, other x-ray methods or laparotomy, 50% of known tumors were accurately localized with sheep anti-CEA. In contrast, 70-80% of known tumor sites were correctly localized with polyclonal monkey anti-CEA antibodies, with monoclonal anti-CEA antibodies or with Fab fragments of the latter. A few previously unknown tumors were detected.

Antibodies, Monoclonal↗

Improved radioimmunolocalization of carcinomas using Fab fragments with anti-CEA specificity.

A model system with human colonic grafts containing carcinoembryonic antigen (CEA) in nude mice was used to improve specificity and sensitivity of the radioimmunolocalization method. Monoclonal antibody MAb I-38S1 and monkey anti-CEA appeared to have high in vitro and in vivo specificity. Fab fragments of MAb I-38S1 improved localization ratios. A reduced time for optimal immunolocalization was obtained with Fab compared with MAb of the same specificity. Combinations of Fab:s, vasoactive compounds or anti-IgG treatment to reduce background levels did not further improve speed of localization or sensitivity.

Alkaline Phosphatase↗

Treatment of patients with metastasizing colo-rectal carcinoma with mouse monoclonal antibodies (Moab 17-1A): a progress report.

Eight patients with metastasizing colo-rectal carcinoma have been treated with Moab 17-1A. Before infusion the antibodies were incubated in vitro with isolated autologous blood mononuclear cells (AMC) enriched for monocytes/macrophages. Treatment was given in repeated courses (2-4 times) up to a maximum amount of 1000 mg Moab 17-1A. Two patients had an objective tumor reduction. In further four patients a period of stable disease varying between 3-6 months on was observed. Therapy was well tolerated. Out of 24 treatment courses only on one occasion an anaphylactoid reaction occurred at the third infusion. All patients developed anti-mouse antibodies of IgG and IgM class with increasing levels during the course of therapy. Repeated tumor biopsies and immunohistochemical analyses showed no antigenic modulation, a weak staining for mouse IgG, no deposits of complement components but no obvious increases in the number of cells infiltrating the tumors 24 h after infusion of antibody-armed AMC.

Adult↗

Preoperative short-term radiotherapy in rectal carcinoma. A preliminary report of a prospective randomized study.

Between 1980 and 1983, 373 patients with clinically resectable rectal adenocarcinoma entered a prospective randomized study aimed to evaluate the effect of short-term preoperative radiotherapy. Protocol violations were identified in 21 instances. Of the remaining 352 patients, 182 were randomized to surgical treatment only (S-group). Immediately, before surgery, 170 patients were irradiated to the pelvic region with 25 Gy (2500 rad) during a 5-day period (RT-group). Of these patients, 59% underwent abdominoperineal excision, 38% anterior resection, and 3% laparotomy only. At surgery distant metastases were discovered in 32 patients (9%). There were no significant differences between the groups in the distribution of age, sex, operative methods, and tumor stage according to the original Dukes' classification. During the follow-up time, ranging between 6 months and 3 years, tumor recurrence occurred in 35 patients, 19 in the S-group and 16 in the RT-group. Fifteen patients in the S-group had pelvic recurrence compared to 10 patients in the RT-group. Distant metastases occurred in six and eight patients, respectively. Two patients in each group had both pelvic and distant recurrence. There was no correlation between tumor recurrence and type of operation. Median time interval from diagnosis to pelvic recurrence was 10 months in the S-group and 16 months in the RT-group. Postoperative complications in the form of wound sepsis were slightly more common in the RT-group. In summary, the applied treatment regimen, is well-tolerated and apparently does not affect the Dukes' stage of the tumor. Although there is no statistically significant difference, there is a trend of less pelvic recurrence in patients receiving preoperative radiotherapy.

Adenocarcinoma↗

Fluorescence methods for measuring the A, B, and H isoantigens on cytological material from bladder carcinoma.

Fluorescence methods for determining ABH isoantigens on transitional cells were developed for the study of cytologic material. Indirect immunofluorescence was used for A- and B-antigens, fluorescein-labeled Ulex Europaeus lectin for the H-antigen. Isoantigens of 151 patients with bladder carcinoma were studied. Patients with a malignant cytology showed deletion in 31/65 cases compared to 12/62 cases when the cytology was benign. Cyto-flow ploidy determinations were abnormal in 41/120 cases measured; cells from 21 of these 41 had isoantigen deletion compared to 25/79 cases with a diploid pattern. The ABH isoantigen deletion shows some relation to malignant cytology, abnormal ploidy and a visible tumor, but is probably an independent parameter.

ABO Blood-Group System↗

Urinary modified nucleosides as tumor markers in cancer of the urinary organs or female genital tract.

Using a sensitive and specific method involving high-performance liquid chromatography, urinary levels of four modified nucleosides--pseudouridine (psi), 1-methylinosine (m1I), 1-methyladenosine (m1A), and 1-methylguanosine (m1G)--were investigated before and after treatment in 31 patients with cancer of the urinary organs or the female genital tract. Before treatment m1I was the most frequently elevated nucleoside (77%). Pretreatment urinary levels of psi, m1I, and m1A in patients with stage 2-4 cancer of the female genital tract were significantly elevated compared to human healthy volunteers (p less than 0.005). Compared with the other nucleosides, psi appeared to correlate more closely with the clinical outcome (progression or regression) of patients with cancer of the female genital tract. In the case of patients with cancer of the urinary organs, m1I followed the clinical outcome better than the other nucleosides measured. Therefore psi and m1I seem to be useful for monitoring genito-urinary cancers.

Adenosine↗

Pseudouridine and uridine in normal kidney and kidney cancer tissues.

The tissue concentrations of a modified nucleoside, pseudouridine, and a normal nucleoside, uridine, were measured with high-performance liquid chromatography. Human kidneys were obtained from five patients with renal cell carcinoma and divided into a noncancerous part and a cancerous part. The pseudouridine concentration in the cancerous part of the kidneys ranged between less than 2-2.8 nmoles/g and in the noncancerous part 4.3-19.4 nmoles/g (mean 10,9 nmoles/g). The uridine concentration in the cancerous and noncancerous parts of the kidney ranged between 19.6-179.1 nmoles/g (mean 110.7 nmoles/g) and 117.5-235.6 nmoles/g (mean 191.5 nmoles/g), respectively. The pseudouridine concentration appeared to be approximately seven times higher in the noncancerous part as compared to the cancerous part of the kidney. In the case of uridine, the difference was less pronounced.

Carcinoma, Renal Cell↗

Serum NCA in bone marrow transplant recipients and its metabolism.

Normal colon and granulocyte antigen (NCA) in serum from 24 patients undergoing bone marrow transplantation (BMT), mostly for leukemic disease, was studied for a period of 0-60 days before/after transplantation. Out of the 23 patients with a take, 20 acquired elevated serum NCA. One patient had a rejection of the transplantation and never showed a rise of NCA values. Thirteen patients were studied in detail; 7 of them had an NCA rise 1-4 days before take, 4 at the day of take and 2 patients 1-4 days later. To investigate the rate of NCA turnover, 125I-NCA was injected into Macaca irus monkeys. One hour after injection, 87% of the injected substance had left the circulation. The prime site of accumulation was the liver. Thereafter, blood NCA decreased at a slower and linear rate. Of the substance seen at the beginning of the second phase 50% had been eliminated after 30 hours. The data support the theory that NCA is produced by the myeloid cells in bone marrow, that it has a rapid metabolism and therefore is of interest as a marker of bone marrow activity in health and malignant disease.

Anemia, Aplastic↗