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Biomedical subjects

J Finke

Publications and source records attributed to J Finke.

At least 109 records · Page 6Linked to original sources
PubMed1996

An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation.

We describe the effects of an aerobic exercise program designed to improve the physical performance of patients undergoing bone marrow transplantation. Twenty patients entered the rehabilitation program, consisting of walking on a treadmill, and carried it out for 6 weeks. Patients started the training program 30 +/- 6 days (range 18-42) post-BMT. By the end of the program we observed a significant improvement in maximal physical performance and maximum walking distance, and a significant lowering of the heart rate with equivalent workloads (P for all significances < 0.001). All participants of the program reached a peak performance (calculated in metabolic equivalents, METs) more than sufficient for carrying out all basic activities of daily living. These results contrast with literature reports indicating that spontaneous recovery of physical functioning after BMT can take many months and that about 30% of patients experience long-lasting impairment of physical performance. We conclude that that fatigue and loss of physical performance in patients undergoing BMT can be corrected with adequate rehabilitative measures.

Adult↗
PubMed1996

Influence of Epstein-Barr virus latent gene expression on the apoptosis-inducing effects of cortisone and 2-chlorodeoxyadenosine (2-CDA) in B-cell lines.

Burkitt's lymphoma (BL) cell lines are heterogenous with regard to phenotype, growth characteristics, Epstein-Barr virus (EBV) latent gene and BCL-2 expression. Previously we have demonstrated that transfection with the EBV genes LMP or EBNA-2 upregulates BCL-2 in B-cell lines. In order to test the functional relevance of these findings, cell lines were examined with regard to their sensitivity towards different apoptosis-inducing agents. BL cell lines transfected with LMP expressed high levels of BCL-2, and were compared with the parental cell line expressing little or no BCL-2. We also studied EBV immortalized lymphoblastoid cell lines (LCL) with high BCL-2 expression and strong resistance towards low serum concentrations. Hydrocortisone (HC) and 2-chlorodeoxyadenosine (2-CDA) were used alone or in different combinations. Cell growth and apoptosis were studied morphologically and by determination of viability and DNA fragmentation. BL cell lines showed different sensitivity towards HC-induced apoptosis, and sensitive cell lines became more resistant towards HC after infection with EBV or transfection with LMP and subsequent upregulation of BCL-2 expression. BL cell lines and LCL were relatively insensitive towards 2-CDA-induced apoptosis, and high concentrations of 2-CDA were necessary, independently of the levels of BCL-2 expression. In contrast to low-grade non-Hodgkin's lymphomas, 2-CDA does not appear to be a valuable drug for the treatment of Burkitt's lymphoma. LMP expression provides resistance towards hydrocortisone-induced apoptosis in vitro, possible through upregulation of BCL-2.

Antineoplastic Agents↗
PubMed1996

Phase I trial of subcutaneous interleukin 3 in patients with refractory malignancy: hematological, immunological, and pharmacodynamic findings.

We conducted a Phase I trial of s.c. recombinant human interleukin 3 (rhIL-3) to evaluate the toxicity, maximal tolerated dose, pharmacokinetics, and in vivo biological effects of this cytokine. Thirty-one patients with refractory cancer were entered into the study between November 1991 and June 1993. Therapy consisted of s.c. rhIL-3 daily for 15 days administered to cohorts of three to nine patients at dose levels of 60-4000 microgram/m2/day. Cycles were repeated at intervals of 28 days. Seventy-five cycles of rhIL-3 were administered (median, two per patient) and the maximal tolerated dose was 2000 microgram/m2/day. Toxicity was moderate, with most patients developing chills, fever, and myalgia. Dose-limiting toxicity consisted of diarrhea (two patients) and headache (one patient). Hematological effects of rhIL-3 included significant dose-related increases of WBC (P < 0.001), neutrophils (P < 0.001), and eosinophils (P < 0.001). Platelet counts and absolute lymphocyte numbers also increased. Various CD3(+) lymphocyte subsets increased; however, lytic activity (natural killer and lymphokine-activated killer) of peripheral blood lymphocytes was not enhanced. Serum levels of the soluble IL-2 receptor increased in a dose-related fashion, and IL-2-induced lymphocyte proliferation also was increased variably. Pharmacokinetic studies were performed in 13 patients, and area under the curve and maximal concentration values increased with increasing rhIL-3 dose levels (P < 0.001) and correlated with maximal changes from baseline in WBC, neutrophils, and eosinophils. rhIL-3 antibodies were detected in 8% of patients by day 29 of cycle 1 but were not neutralizing. rhIL-3 is well tolerated when administered s.c. and has reproducible hematological and immunological effects. The pleiotropic effects of this cytokine on various in vivo biological parameters were demonstrated clearly. Further studies of its immunoregulatory effects are warranted.

Adult↗
PubMed1995

Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow.

Infection of hematopoietic progenitor cells with the human cytomegalovirus (HCMV) has been proposed as an explanation for the cytopenias associated with HCMV-related disease. To test this hypothesis, CD34+ cells, which include the hematopoietic progenitors, as well as mature leukocyte populations were purified on a fluorescence-activated cell sorter and analyzed for HCMV DNA by polymerase chain reaction (PCR). A total of 33 samples from 31 immunosuppressed as well as immunocompetent HCMV-seropositive individuals were studied. CD34+ cells were PCR-positive in four of seven bone marrow aspirates from allogeneic bone marrow transplant recipients, in three of eight aspirates from patients with acquired immunodeficiency syndrome, and in the first of two bone marrow samples from an immunocompetent patient with primary HCMV disease. CD34+ cells purified from peripheral blood for autologous and allogeneic transplantation were also analyzed, and 4 of 13 samples were HCMV DNA-positive. Interestingly, two of the four HCMV-positive samples were from healthy allogeneic donors. Among the mature leukocyte populations, the monocytes were most frequently found to be HCMV DNA-positive. No HCMV DNA was detected in the total bone marrow leukocytes of 13 healthy seropositive bone marrow donors or in the CD34+ cell fraction of three further seropositive donors. In conclusion, the data provide strong evidence that CD34+ hematopoietic progenitor cells can be infected with HCMV in immunosuppressed patients, while this cell population was not identified as a major viral reservoir in healthy HCMV-seropositive individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1995

T cells infiltrating non-Hodgkin's B cell lymphomas show altered tyrosine phosphorylation pattern even though T cell receptor/CD3-associated kinases are present.

Although tumor infiltrating lymphocytes (T-TIL) from B cell non-Hodgkins lymphoma patients contain tumor-reactive T cells, they display poor proliferation and IFN-gamma production when stimulated through the TCR-CD3. To determine if there was altered signaling linked to TCR-CD3 ligation, tyrosine phosphorylation was examined in T-TIL because it represents an early and critical event in T cell activation. After stimulation with anti-CD3 Ab, Western blotting with anti-phosphotyrosine showed reduced phosphorylation in T-TIL when compared with peripheral blood-derived T cells from normal individuals. The altered phosphorylation was not due to the reduced expression of signaling elements linked to the TCR-CD3 complex. T-TIL expressed normal levels of CD3 epsilon, TCR zeta chain, and the three tyrosine kinases, p56lck (Lck), p59fyn, and ZAP-70. However, in T-TIL, anti-Lck Ab reacted with a 60-kDa protein, which appears to be the phosphorylated form of Lck. Binding of anti-Lck Ab to the 60-kDa protein was blocked by Lck peptide. In addition, anti-Lck Ab immunoprecipitated a phosphorylated 60-kDa protein from gamma-32P-labeled T-TIL that was not seen in normal resting T cells. In vitro kinase assay studies also demonstrated that TCR-CD3 engagement increased the kinase activity of Lck in normal T cells but not in T-TIL. These results suggest that although T-TIL from B cell non-Hodgkins lymphoma patients contain the signal transduction molecules associated with TCR-CD3 activation pathway, they are impaired in tyrosine phosphorylation and Lck activity, which may contribute to the functional defects of these cells.

Humans↗
PubMed1995

Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor-infiltrating lymphocytes.

The progression of tumors such as renal cell carcinoma (RCC), despite the presence of substantial lymphocytic infiltrates (TIL), suggests that the ability of the local immune response to control tumor growth is impaired. Cytokine gene expression was examined to further investigate the nature of this response. Initial studies were performed with frozen tumors using PCR-assisted mRNA amplification with cytokine-specific primers for interleukin 10 (IL-10), interleukin 2 (IL-2) and interferon-gamma (IFN-gamma). IL-2 mRNA was not detected, despite the presence of T cells as defined by the expression of CD3 gamma mRNA. In contrast, mRNA for IFN-gamma was expressed in 4/9 and for IL-10 in 5/9 tumors. To confirm this, 5 fresh tumor specimens were examined, and PCR demonstrated that IL-10 mRNA was detectable in 4/5 tumors from which RNA was isolated at the time of nephrectomy. In these experiments multiple cycles and dilutions were employed to semi-quantitate the expression of IL-10. To identify potential sources of this cytokine in the tumor bed, IL-10 mRNA expression in freshly isolated lymphocytes and tumor cells, TIL lines, cultured RCC and established RCC lines was examined. Our studies demonstrate that within the tumor TIL may be one source of IL-10. Lymphocyte-enriched populations from 4/5 tumors expressed IL-10 mRNA as did 4/6 freshly isolated tumor cell preparations. IL-10 gene expression was not detected, however, in tumor cells after one passage in vitro in short-term cultured RCC tumor cells (passages 2-5) or in established RCC tumor cell lines. Finally, 4/9 CD4+ and 2/5 CD8+ TIL lines expressed IL-10 mRNA either constitutively or after stimulation with anti-CD3 antibody. This finding was associated with IL-10 production in vitro. Our studies demonstrate that IL-10 mRNA is frequently present in RCC tumors and may originate from the tumor-infiltrating mononuclear cell population.

Base Sequence↗
PubMed1995

[Psychotherapy in the psychiatric clinic--an empirical study of the expectations of patients].

Before admission to in-patient psychotherapeutic treatment 202 patients with schizophrenic or neurotic orders, partly with secondary alcohol or substance addiction, were investigated with a questionnaire concerning patients' expectations of psychotherapy: targets, expectations of therapeutic attitude and technique as well as therapeutic procedure (individuals or group therapy). The results are correlated with sociodemographic data and psychiatric disorders and compared with the patients who were not admitted to therapy and the results after discharge. Conclusions are made with regard to indication and adaptive patient-centered therapeutic proceeding.

Adult↗
PubMed1995

[How can acceptance by psychiatric patients of group psychotherapy be improved? An empirical study of the effect of combined individual and group psychotherapy on attitude to group psychotherapy].

This study investigates whether the sceptic attitude of many psychiatric patients to group therapy can be improved by a combined individual and group therapy program. The investigation was made on 50 patients, most of them with neurotic disorders, partly with secondary alcohol or substance abuse as well as some schizophrenic patients. Before admittance to the psychotherapy program enquiries were made by means of a questionnaire, about what subject they would like to speak in the individual or group therapy sessions. The results differ significantly dependent on sociodemographic and illness related factors. A second examination after discharge reveals an ameliorated attitude concerning group therapy in nearly all central themes. Thus, one of the important goals of in-patient psychotherapy has been achieved to improve patients ability to receive out-patient group therapy.

Adult↗
PubMed1994

T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report.

Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-kappa B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.

Base Sequence↗
PubMed1994

Comparison of different ribozymes for efficient and specific cleavage of BCR/ABL related mRNAs.

In chronic myelogenous leukemia (CML) the reciprocal translocation of the long arms of chromosomes results in the formation of the unique BCR/ABL fusion gene which is believed to play a crucial role in the pathogenesis of CML. Different short synthetic ribozyme constructs were compared with regard to their efficiency to cleave the BCR/ABL target RNA. In the CML cell line K562 we were able to inhibit the p210BCR/ABL synthesis by a ribozyme which was about twofold more effective than the corresponding antisense molecule.

Base Sequence↗
PubMed1994

Detection of chromosome 11q23 involving translocations by pulsed field gel electrophoresis.

Translocations involving chromosome band 11q23 are associated with acute lymphocytic and myelomonocytic leukemias with poor clinical prognosis. Pulsed-field gel electrophoresis (PFGE) was used to characterize the breakpoint region that has been mapped within a 300-kb fragment between the genes CD3G and PBGD. Using CD3G as a marker on SfuI-restricted DNA separated by PFGE, we detected a rearrangement involving 11q23 in the cell line B1 with a t(4;11) and in the leukemic cells of two patients, one with a t(2;11) and one with a t(11;19). In comparison, lymphoblastoid cell lines established from normal peripheral blood lymphocytes of these two patients had a normal karyotype and showed germline configuration, thus excluding RFL polymorphisms. Digestion of DNA with BssHII or SalI showed heterogeneity of 11q23 involving breakpoints. A rearrangement in the t(4;11) containing lymphoma cell line Karpas422 was seen only with the chromosome 4 probe KIT on SalI-digested DNA. PFGE is a reliable method for the mapping and detection of complex breakpoint regions. The breakpoints on 11q23 involve different introns of the highly spliced HRX/ALL-1/MLL gene.

Acute Disease↗
PubMed1994

Phase I trial of cisplatin, WR-2721, and the murine monoclonal antibody R24 in patients with metastatic melanoma: clinical and biologic effects.

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.

Adult↗
PubMed1994

Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor: clinical and immunomodulatory effects.

PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been demonstrated to control the growth, differentiation, and function of mononuclear phagocytes. Preclinical studies have indicated antitumor effects, and therefore a phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity and hematologic and immunologic effects were investigated. PATIENTS AND METHODS: rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8 through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting toxicity included thrombocytopenia (two patients) and iritis (one patient) occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose-related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes after in vitro stimulation with lipopolysaccharide, and increased expression of TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated that the systemic clearance rate of M-CSF increases during week 1 of therapy, resulting in lower blood levels of M-CSF during the second week of therapy. CONCLUSION: rM-CSF can be safely administered to patients, and has biologic activity on peripheral-blood monocytes.

Adult↗
PubMed1994

BCL-2 induction is part of the strategy of Epstein-Barr virus.

Epstein Barr virus can infect B lymphocytes and epithelial cells. Epithelial cells present the natural reservoir for the virus in man. In vitro, infected cells harbor the virus predominantly in a latent state with the expression of a set of nuclear (EBNA 1-6) and latent membrane genes (LMP 1-2) and virus-transformed B cells grow as permanently immortalized lymphoblastoid cell lines, that show increased resistance to various growth inhibiting factors. Here we show that the lymphoma-associated oncogene BCL-2 is upregulated by different latent Epstein-Barr virus genes in B lymphocytes as well as keratinocyte cell lines. Thus, the induction of BCL-2 gene expression seems to be part of the survival strategy of the virus independently of the host cell infected.

B-Lymphocytes↗
PubMed1994

[Change in causal attributions and coping caused by inpatient client-centered psychotherapy].

During 3-month client-centered hospital treatment 108 patients with neurotic depression, anxiety disorders and other neuroses (DSM-III-R) recovered from depressivity (Giessen-Test, MES), negative attributional styles and regressive coping (KCF). Gains were maintained over follow-up one and two years after therapy. Not only cognitive, but also rogerian psychotherapy leads to significant increment in cognitive coping efforts, even when grade of depressivity is regarded. Attributional style and coping strategies depended on grade of depressivity and status of patient (admission or follow-up); cognitions did not discriminate dysthymic (depressive) patients from other neurotic disorders.

Adaptation, Psychological↗
PubMed1994

[Malignant meningeal "histiocytosis"].

Two cases of patients with unusual pleomorphic tumors in the meninges are reported. Histologically and immunohistologically, the tumor cells may be histiocytic in appearance. Computed tomography and magnetic resonance imaging scans, however, revealed no lesions in the parenchyma or in the meninges. The cytological examination of the cerebrospinal fluid revealed only a light lymphocytic reaction without tumor cells in both cases and thus led to misinterpretations as meningoencephalitis. One patient presented psychiatric symptoms. Related clinical problems and the possible histogenesis of the tumors are discussed.

Adult↗