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Biomedical subjects

L Bergmann

Publications and source records attributed to L Bergmann.

At least 91 records · Page 5Linked to original sources
PubMed1994

Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients.

Serum levels of soluble CD14 were elevated in HIV-infected asymptomatic patients or those with lymphadenopathy (CDC II/III) 2.9 +/- 0.8 mg/l compared with normal controls with 2.2 +/- 0.47 mg/l, P < 0.001. A further rise was seen in patients with ARC (CDC IVA) 3.8 +/- 1.1 mg/l, P < 0.01 and patients with AIDS (CDC IVB-D) 5.7 +/- 2.5 mg/l, P < 0.01. Although absolute numbers of CD14+ cells decrease in the AIDS group, the percentage of CD14+ monocytes did not change. In contrast, levels of soluble T cell antigens sCD4 and sCD8, which are higher in HIV-infected patients compared with normal subjects, showed no increase with disease progression. Serum levels of sCD14 were correlated positively with beta 2-microglobulin levels (rs = 0.63, P < 0.0001). Whereas the percentage of CD14+ monocytes did not change, an increase in monocytic CD14 expression in HIV-infected patients was observed (P < 0.01). The percentage of a monocyte subset expressing both CD14 and CD16 increased from 6% in normal healthy persons to 13% in HIV-infected patients (P < 0.001), and did not vary between the HIV patient groups. Incubation of cultured peripheral blood monocytes with azidothymidine had no effect on either normal or LPS-induced or IL-4-inhibited sCD14 release in vitro. Therefore, an effect of AZT on sCD14 serum values in vivo is considered to be unlikely. Our data further provide evidence that monocytes/macrophages are engaged in HIV infection.

Adult↗
PubMed1994

The expression of the Wilms' tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells.

The Wilms' tumor gene (wt-1) is expressed in the developing fetal kidney, gonads and in Wilms' tumors. Recently, the expression of wt-1 in leukemia-derived cell lines and cases of acute leukemias (AL) was reported. The present study was designed to investigate the potential of wt-1 as genetic marker for acute myelocytic leukemias (AML). Blast cells from 52 patients with AML, 14 patients in complete remission (CR) and four leukemic cell lines were examined for expression of wt-1 mRNA. Peripheral blood mononuclear cells (PBMNC) and bone marrow (BM) from 13 healthy persons were used as negative controls. RNA of the wt-1 gene was expressed in 41/52 (79%) patients with previously untreated AML. The majority of the 14 patients studied in CR lost wt-1 expression. In three out of the four patients in CR reappearance of wt-1 expression preceded relapse of the disease. In three of the four tested cell lines wt-1 specific transcription was demonstrated. No correlation to FAB classification, immunophenotype or response to treatment was found. Our experiments indicate wt-1 expression in the majority of AML, but not in bone marrow or PBMNC of healthy controls. Therefore, wt-1 expression may be associated with the presence of malignant blast cells and the analysis of wt-1 gene expression via PCR may be a sensitive method for the detection of leukemic blast cells.

Adult↗
PubMed1994

How can we share the portal blood inflow in auxiliary partial heterotopic liver transplantation without portal hypertension?

BACKGROUND: Auxiliary partial heterotopic liver transplantation (APHLT) may be an attractive treatment for fulminant hepatic failure in which recovery of the host liver is expected. We investigated the functional relationship between an auxiliary heterotopic partial liver graft and the host liver with or without portal hypertension in pigs. METHODS: Sixteen pigs underwent hepatic artery ligation and APHLT; in addition, various degrees of portal hypertension were created by banding the host portal vein. The pigs were randomly divided into three groups: group A (n = 5), the host portal vein was not banded; group B (n = 6), the host portal vein was banded to make the host portal pressure higher than that of the graft by 2 mm Hg; and group C (n = 5), the host portal vein was banded to make the host portal pressure the same as that of the graft. RESULTS: All of the pigs in group A had necrotic and atrophied grafts with graft portal vein thrombosis and well-hypertrophied host livers. All of the pigs in group B had well-functioning grafts and necrotic and atrophied host livers. Three of the five pigs in group C had well-functioning grafts and host livers, although the remaining two pigs exhibited the same results as those in group A. CONCLUSIONS: APHLT could be a valuable alternative treatment for temporary support in fulminant hepatic failure. However, if the recipient does not exhibit portal hypertension, the host portal vein should be banded to make the host portal pressure at least the same as that of the graft.

Animals↗
PubMed1993

Plasminogen depletion during streptokinase treatment or two-chain urokinase incubation correlates with decreased clot lysability ex vivo and in vitro.

The relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/l. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 +/- 8% after 5 min to 21 +/- 8% at 10 min and was significantly lower (8 +/- 9%, p < 0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p < 0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

Amino Acid Sequence↗
PubMed1993

Daily alternating administration of high-dose alpha-2b-interferon and interleukin-2 bolus infusion in metastatic renal cell cancer. A phase II study.

BACKGROUND: Both interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) have some efficacy in renal cell cancer (RCC) as single agents. Additionally, there is some evidence for additive or synergistic antitumoral activity of IL-2 and alpha-IFN in vitro and possibly in vivo. Based on these data, the authors initiated a Phase II trial with a combination of recombinant IL-2 (rIL-2) and recombinant alpha-IFN (alpha-rIFN) in advanced RCC. METHODS: Thirty-six assessable patients with metastatic RCC were entered in this Phase II trial using a daily alternating schedule of alpha-rIFN and rIL-2. Over a period of 14 days, the patients received daily alternating treatment with 10 x 10(6) IU/m2 of recombinant alpha-2b-interferon subcutaneously and 18 x 10(6) IU/m2 of rIL-2 as a 1-hour intravenous infusion. This treatment schedule was repeated every sixth week up to a maximum of four cycles. After the second cycle, patients were examined for response. Patients with stable disease or better received two additional cycles of therapy. Patients with progressive disease were available for other strategies. RESULTS: Thirty-six patients entered the trial and were assessable for toxic effects. Thirty of 36 patients completed at least two cycles and were assessable for response. Nine patients achieved an objective response: 2 had complete responses (CR) and 7 had partial responses (PR). Three patients had a minor response. No effect was observed in patients with local relapse or bone metastases. A relapse-free survival length of 6 months or longer was seen in both patients with CR (12, 23 + months) and in four of seven patients with PR (6, 7, 12, 12 months). The toxicity was moderate and included fever and nausea in most patients, and hypotension, fatigue, skin rash, and arthralgia in a minority of the patients. No Grade 4 and only occasionally Grade 3 toxicity was observed. Fluid retention was negligible. The monitoring of immunologic parameters showed a significant rebound lymphocytosis including cytotoxic (CD56+) cells; in responders the peak of lymphocytosis occurred up to 1 week later than in nonresponders. Peripheral lymphocytes obtained after therapy showed only a slight increase of natural killer cell and lymphokine-activated killer cell activity. During therapy, there was a great release of secondary cytokines as tumor necrosis factor-alpha, gamma-interferon, and interleukin-6, with a peak level 2-4 hours after rIL-2 infusion. CONCLUSIONS: In conclusion, daily alternating administration of alpha-rIFN and rIL-2 is effective in RCC with less toxicity, and the response rate is comparable to those of other immunotherapeutic schedules, including adoptive immunotherapeutic schedules, including adoptive immunotherapy and combinations of high-dose IL-2 and alpha-IFN.

Aged↗
PubMed1993

Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma. Comparison of two phase II trials.

BACKGROUND: Interferon-alpha (IFN alpha) and interleukin-2 (IL-2) are active agents against malignant melanoma. There is, however, no consensus on the optimal dosing schedule of both drugs. This is a report of two sequential immunotherapy trials in patients with metastatic melanoma using two different IL-2 dosing schedules. METHODS: Schedule A consists of IFN alpha, 10 million U/m2/day subcutaneously for 5 days, followed by continuous intravenous infusion of IL-2, 1 mg/m2/24 hours for 5 days. Schedule B consists of the same dose of IFN alpha, but a modified regimen of IL-2. To improve the induction of high-affinity IL-2 receptors, the initial IL-2 dose was increased (1 mg/m2/6 hours, followed by 1 mg/m2/12 hours, and 1 mg/m2/24 hours). To reduce toxicity, the dose was reduced thereafter to 0.25 mg/m2/24 hours for the following 3 days. Both regimens were repeated after 4 weeks. RESULTS: 27 patients were treated with schedule A with a response rate of 18% (1 complete response [CR], 4 partial responses [PR]), 95% confidence interval, 6-36%. The response rate in 27 patients treated with schedule B was 41% (3 CR, 8 PR), 95% confidence interval, 22-61%. Severe, often dose-limiting toxicity was associated with IL-2 in schedule A, particularly hypotension and fluid retention. Toxicity was reduced significantly in schedule B. Maximal serum levels of soluble CD25 were 17,022 +/- 13,070 U/ml in schedule A, and 31,148 +/- 4227 U/ml in schedule B (P < or = 0.01). Serum levels of TNF alpha were significantly lower in schedule B than in schedule A, as were the side effects. CONCLUSIONS: Toxicity of IL-2 is reduced by modifying the schedule of administration, which also enhances the immunologic response and appears to increase the response rate.

Adult↗
PubMed1993

[Pleomorphic T-cell lymphoma. The diagnostic problems, therapeutic possibilities and infection-induced complications].

A 30-year-old man complained of high fever, resistant to antibiotics, and progressive loss of strength for five weeks. The peripheral blood showed pancytopenia (leucocytes 2200/microliters, platelets 45,000/microliters, haemoglobin 10.7 g/dl). There was also hepatosplenomegaly, abdominal lymph node enlargement, pleural and pericardial effusions and slight excess of lymphocytes in the cerebrospinal fluid. Histological examination of the bone marrow suggested a small-cell pleomorphic T-cell lymphoma, but Hodgkin's disease was also considered. Splenectomy was performed to confirm the diagnosis and treat the pancytopenia. The blood count rapidly returned to normal and the suggestion of Hodgkin's disease was excluded. Intensive chemotherapy (BMFT-ALL protocol) was followed by regression of nearly all the abnormalities, but marrow infiltration persisted. This treatment was discontinued after phase II of induction. After an intercurrent cytomegalovirus infection maintenance treatment with alpha-interferon (up to 5 million units daily) was started. The partial remission remained stable for 22 months. The lymphoma then relapsed but was held in check by further chemotherapy (Dexa-PAMB protocol). For the past 11 months the patient has remained in stable partial remission on treatment with alpha-interferon (3 million units every other day). Frequent infections (sinusitis, diarrhoea, abscess) require close supervision.

Adult↗
PubMed1993

Aggressive chemotherapy combined with G-CSF and maintenance therapy with interleukin-2 for patients with advanced myelodysplastic syndrome, subacute or secondary acute myeloid leukemia--initial results.

Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections. Until now, 19 patients with high-risk AML have been entered. The CR rate is 47%, with only one death during induction. Patients achieving CR are randomized to receive either high-dose or low-dose interleukin-2 to eliminate residual leukemic cells and to prolong the duration of remission.

Adult↗
PubMed1993

Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia.

BACKGROUND: Fludarabine monophosphate is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) with response rates, including hematological complete remissions, of 50%-60% in previously treated and 75%-80% in previously untreated patients. PATIENTS AND METHODS: Here, the clinical experience with and side effects of fludarabine are reported in 19 patients with refractory CLL (17 B-CLL, 2 T-CLL). All patients were pretreated with one to four different regimens and had progressive disease. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute intravenous infusion. This course was repeated every fifth week. Dosage and time course were adapted to toxicity. RESULTS: 12/18 (67%) evaluable patients achieved partial remissions (PR), 1/18 (6%) had stable disease (SD) and 5/18 (28%) were progressive. The median duration of partial remission until relapse or death was 6 months. Most responses to fludarabine occurred within two treatment courses. Major toxic effects included infections in 11 patients and nausea in 8 (mainly grade 1). Meanwhile, three patients died of progressive disease and 8 of pneumonias or other infections. Two patients had pneumocystis carinii pneumonias and one an aspergillus pneumonia. The high infection rate may be due not only to hypogammaglobulinaemia or fludarabine-induced granulocytopenia but also to a remarkable decrease of CD4(+)-cells during fludarabine therapy. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. CONCLUSION: It is concluded that fludarabine is effective even in patients with advanced chronic lymphocytic leukemia refractory to multiple chemotherapy regimens. However, fludarabine has a remarkable suppressive effect on T-lymphocytes, predominantly CD4(+)-lymphocytes. Long-term antibiotic prophylaxis is recommended.

Adult↗
PubMed1992

Cytotoxic action of IL-1 beta against pancreatic islets is mediated via nitric oxide formation and is inhibited by NG-monomethyl-L-arginine.

IL-1 beta has been previously shown to act as a cytotoxic agent in islets. Here we show by electron microscopy of alginate encapsulated islets, that islet cell lysis is induced by culturing islets for 24 or 48 h in the presence of IL-1 beta. The extent of lysis depends on the IL-1 beta concentration and is slightly enhanced by the addition of TNF-alpha. Cells can be protected from lysis by NG-monomethyl-L-arginine. Lysis is paralleled by an increase in nitrite concentration in culture supernatants of whole islets but not in supernatants of isolated endocrine cells. The results indicate that IL-1 beta toxicity occurs via inducing in non-endocrine islet cells the synthesis and release of nitric oxide, which has been shown earlier to be highly toxic for islet cells.

Animals↗
PubMed1992

Rapid cytokine release in cancer patients treated with interleukin-2.

Serum concentrations of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) were determined by commercially available enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in cancer patients treated with recombinant IL-2 (rIL-2) either as 1-h infusion (3 or 5 x 10(6)/m2) or continuous intravenous infusion for 5 days (3 x 10(6)/m2/day). A significant increase of TNF-alpha and IL-6 serum levels was observed in each patient. One-hour infusion of IL-2 induced a very rapid secretion of TNF-alpha, IL-6 and IFN-gamma with considerably higher peak levels than during IL-2 continuous intravenous infusion. IFN-gamma was released into the blood of all patients receiving IL-2 1-h infusion, but only occasionally during or after IL-2 continuous intravenous infusion. Neither IFN-alpha nor IL-1 were detectable in the serum before, during, or following IL-2 treatment in all patients studied. The kinetics of IL-2 after 1-h infusion fitted to a two-compartment model, suggesting the synthesis of considerable amounts of endogenous IL-2. Following IL-2 1-h infusion, rising TNF-alpha serum levels preceded the increase of serum IFN-gamma or IL-6. The serum peak levels of IFN-gamma and IL-6 decreased rapidly with a half-life of 0.29 to 2.5 h. The concentration time profiles of TNF following 1-h infusion of IL-2 demonstrated a considerably longer half-life than that of intravenously administered recombinant TNF as done in other studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗
PubMed1991

High release of tumor necrosis factor alpha, interferon gamma and interleukin-6 by adherent lymphokine-activated killer cells phenotypically derived from T cells.

Adherent lymphokine-activated killer cells (A-LAK) are highly potent cytotoxic cells, which are shown to be derived not only from natural killer (NK)/K cells but phenotypically also from T cells. The generation and phenotypical and functional characterisation of these T-cell-derived A-LAK are described. In contrast to non-adherent cells (NA-LAK) and unseparated LAK (UN-LAK), these mostly CD3+ CD56+ CD8+ cells display a high degree of expansion following initial interleukin-2 (rIL-2) activation and further culturing in autologous conditioned medium. A comparison of cytotoxic activities of cultured cells reveals a significantly higher oncolytic ability of A-LAK cells against both K562 and Daudi cells than that of cultured controls of NA-LAK and UN-LAK. In addition, A-LAK are characterised by a marked endogenous cytokine release of interferon gamma, tumour necrosis factor alpha and IL-6 as well as by their shedding of p55 IL-2 receptor after exposure to IL-2. The results demonstrate A-LAK to be the lymphocyte subpopulation with the most cytotoxic activity and endogenous cytokine release after exposure to IL-2. The improvement of techniques for long-term cultures may be of interest for future therapeutic approaches.

Cell Adhesion↗
PubMed1991

Cytotoxic activity and phenotypic characteristics of lymphocyte subsets after therapy of cancer patients with interleukin-2.

After a 5-day period of continuous intravenous infusion of recombinant interleukin 2 (rIL-2) in seven patients with malignant melanoma or gastric or pancreatic cancer, different lymphocyte subsets were separated from patients' blood and tested ex vivo for cytotoxic activity against various tumour cell lines. Lytic activity was mediated by CD3+CD56+, CD3-CD56+, CD3-CD2+ and CD8+CD56+ lymphocytes. No cytotoxic activity could be observed within the CD3+CD56-, CD3+CD2+ or CD4+ T cell subsets. To characterize CD56+ cytotoxic cells further, the expression of other antigens on this population was analysed before and after IL-2 therapy. CD3, CD4, CD16 and CD57 antigens were weakly expressed, and the IL-2 receptor (CD25) was not detectable on these cells either before and after treatment with IL-2. In contrast, increased expression of CD2. CD8 and HLA-DR antigens occurred following therapy. The divergence of CD3 and CD8 antigen expression after IL-2 therapy was caused by an increase in CD3-CD8+ cells, detectable as a low-density CD8+ subset. This study shows that cytotoxic activity of in vivo IL-2-activated killer cells is predominantly, but not exclusively, mediated by CD3-CD56+ lymphocytes, partially coexpressing the CD8 antigen and lacking the expression of CD16 antigens.

Antigens, CD↗
PubMed1991

Cisplatin, etoposide, ifosfamide, vincristine and bleomycin combination chemotherapy for far advanced testicular carcinoma.

Forty-eight patients with advanced testicular cancer, defined as abdominal mass greater than 10 cm, mediastinal mass greater than 5 cm, more than 20 lung metastases, or visceral organ involvement were treated with an intensive, alternating five-drug regimen consisting of cisplatin 50 mg/m2 d 1-3, etoposide 170 mg/m2 d 1-3, ifosfamide 5 g/m2 d 15, vincristine 2 mg weekly, bleomycin 15 mg/m2 weekly, q d 28. Thirty-four (71%) of the patients attained tumor-free status. This was achieved by chemotherapy alone in 14 patients and by surgical resection of residual disease in the remaining 20 patients (histology of resected tissue: necrosis 12, mature teratoma 7, viable carcinoma 1). Patients with pure seminoma responded better than patients with nonseminoma (CR 100% vs. 67%, respectively). In a univariate analysis only the value of HCG (less than vs greater than 10,000 U/L) and the number of involved organ sites (less than or equal to 2 vs greater than to 2) had significant influence on the response rate. After a minimum follow-up of 24 months 3 patients (9%) have relapsed. The survival rate is 76% after 36 months, with 61% remaining disease-free. Though this intensive regimen might bestow some of the therapeutic advantages of standard three-drug protocols in far advanced testicular cancer, the results are still less than optimal and warrant the exploration of new therapeutic strategies.

Adolescent↗