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E Klein

Publications and source records attributed to E Klein.

At least 145 records · Page 8Linked to original sources
PubMed1994

Endogenous TGF-beta contributes to the induction of the EBV lytic cycle in two Burkitt lymphoma cell lines.

A low proportion of cells in the BL lines P3HR-I and Akata enter spontaneously into the EBV lytic cycle, detectable by the expression of early antigens (EA). We found that both lines produce the active and inactive forms of TGF beta. It was shown earlier that a larger number of cells can be induced to enter the lytic cycle by exposing P3HR-I to phorbol esters and n-butyrate and the surface IgG-positive Akata cells to anti-IgG. We now show that the same treatments raise the level of active TGF beta release. Exposure to anti-TGF beta antibodies reduced EA induction by 75-85%. Our results indicate that induction of the viral productive cycle by the above-mentioned reagents is at least partly dependent on the activation of endogenous TGF beta production.

Burkitt Lymphoma↗
PubMed1994

Identification of wild-type and mutant p53 peptides binding to HLA-A2 assessed by a peptide loading-deficient cell line assay and a novel major histocompatibility complex class I peptide binding assay.

Mutations of the p53 gene are the most frequently observed genetic changes in human cancers; often leading to an overexpression of the wild-type (wt) p53 protein. Demonstrable T cell reactivity against tumor cells overexpressing wt or mutant p53-derived peptides could support the application of such epitopes in cancer immunotherapies. As the binding of peptide to MHC class I molecules is a prerequisite for antigen-specific T cell recognition, we evaluated the ability of wt and mutant p53 peptides to bind to HLA-A2.1 using two independent flow cytometry-based assay systems, the T2 major histocompatibility complex (MHC) class I peptide stabilization assay (stabilization assay) and the peptide-induced MHC class I reconstitution assay (reconstitution assay). The twenty selected wt sequences each conformed to the previously reported HLA-A2.1 peptide binding motif. Seven of the wt p53 and 2/13 mutant p53 peptides derived from the previously chosen wt peptides bound to HLA-A2.1 in both the stabilization and the reconstitution assays. An additional six wt and six mutant p53 peptides, presumably exhibiting lower affinity for HLA-A2.1, were identified only in the reconstitution assay. Those p53 peptides binding HLA-A2.1 may provide useful immunogens for the generation of HLA-A2.1-restricted cytolytic T lymphocytes in vitro and in vivo.

Amino Acid Sequence↗
PubMed1994

Cardiac metastasis of liposarcoma.

The authors describe a retroperitoneal liposarcoma with secondary involvement of the left ventricle. Therapy has been disappointing, and is guided by the nature of the primary tumor, previous therapy, extent of metastatic spread, and feasibility of cardiac resection. In selected patients whose primary tumor is well-controlled and progressing slowly, with no evidence of widespread disease, resection of the cardiac metastases can be performed when technically feasible.

Echocardiography↗
PubMed1994

Fungal infections in liver transplant recipients.

A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious non-fungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P < 0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P = 0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.

Adolescent↗
PubMed1994

Cytotoxic susceptibility and defective MHC class I expression do not correlate with mutation of p53 in human carcinomas.

Twenty-nine samples of ex vivo ovarian and lung carcinomas were investigated for the relationship between the presence of mutated protein 53 (mp53) and cytotoxic susceptibility. Unaltered expression of MHC class I alleles was required for the cytotoxic susceptibility of tumour cells to the autologous ex vivo blood lymphocytes, i.e. all 4 sensitive tumours belonged to the group of 11 tumours without defect in MHC class I expression. In contrast, the susceptibility did not correlate with the presence of mp53, i.e. cases with mp53 were randomly distributed between the sensitive and resistant tumours (2/4 and 10/17 respectively). There was no correlation either between the p53 mutation and down-regulation of MHC class I alleles. The results suggest that in these tumours the mutated p53 is not the source of immunogenic peptides and that the lack of recognition of the tumours with mp53 is not caused by a defect in the expression of MHC class I molecules.

Adenocarcinoma↗
PubMed1994

Generation of HLA-B55 restricted T lymphocyte mediated cytotoxicity against autologous LCL.

The lymphocytes of one HLA-A11 positive individual (A1, A11, B49, B55) were stimulated in vitro with the autologous EBV transformed lymphoblastoid cell line (LCL). The culture contained HLA-A1, A11 and B55 restricted, LCL selective cytotoxic T cells (CTLs). In the T cell culture stimulated four times, the lysis of A11 and B55 carrying targets suggested that the subsets of the two latter CTL types had similar size. After further stimulations the B55 restricted CTLs were enriched in the culture. Earlier results suggested that in HLA-A11 positive individuals the A11-restricted LCL-selective CTL subset dominates. The sensitivity of a target panel including Burkitt lymphoma (BL) lines suggested that the peptide presented by the B55 molecule differs in A and B type EBV strain carrying cells.

Cell Line, Transformed↗
PubMed1994

Biphasic effect of transforming growth factor-beta on Epstein-Barr virus-induced activation of human tonsillar B cells.

Transforming growth factor-beta (TGF-beta) is known to inhibit mitogen-induced proliferation of human B lymphocytes. Earlier results showed that activation of B cells by Epstein-Barr virus (EBV) was also inhibited by TGF-beta. On the other hand, TGF-beta could enhance the transformation of EBV-infected B-cell cultures. In the present set of experiments, we have confirmed the inhibitory effect of TGF-beta on the EBV-induced blastogenesis and found lower expression of CD23 in the treated cultures. However, cells which escaped inhibition and entered in the blast stage expressed a higher level of CD23 molecules. The elevation of CD23 in the TGF-beta-treated cultures was more marked at a time when the cell size profiles of the control and treated cultures were similar. In view of the function of the CD23 molecule as an autocrine growth factor, its increased expression is consistent with previous findings on TGF-beta-mediated enhancement of the transformation of B-cell cultures. The occurrence of growth inhibitory and growth stimulatory effect of TGF-beta on the same cell type has been observed in several other systems as well.

B-Lymphocytes↗
PubMed1994

The impact of adjuvant nephrectomy on multimodality treatment of metastatic renal cell carcinoma.

Multimodality treatment of metastatic renal cell carcinoma with biological response modifiers and cytoreductive surgery has produced durable responses. The timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We reviewed the treatment of 62 patients with metastatic renal cell carcinoma and primary tumors in place who qualified for multimodality treatment comprising adjuvant nephrectomy and biological response modifier protocols at our institution between 1987 and 1992. Of the patients 37 were scheduled to undergo initial adjuvant nephrectomy followed by biological response modifier therapy. A total of 25 patients underwent initial biological response modifier therapy with planned delayed adjuvant nephrectomy if a response to treatment was demonstrated. Of the 37 patients undergoing initial adjuvant nephrectomy, 8 (22%) were unable to enter induction of immunotherapy because of perioperative complications (1), medical contraindications (2), tumor progression (4) or death (1). Three patients in the initial adjuvant nephrectomy group (8%) had a partial response and the median survival in this group was 12 months (range 1 to 57). In the initial biological response modifier group 3 patients (12%) with an objective response (2 complete and 1 partial) to biological response modifier therapy underwent nephrectomy. The median survival for the initial biological response modifier group was 14 months (range 1 to 48). These results add to our understanding of the impact of adjuvant nephrectomy on patients with metastatic renal cell carcinoma considered for immunotherapy protocols.

Adult↗
PubMed1994

Complications of nephron sparing surgery for renal tumors.

The technical results of 259 nephron sparing operations for renal cell carcinoma or renal oncocytoma were reviewed. Local or renal related complications occurred after 78 procedures (30.1%). The incidence of complications was less for operations performed after 1988 (22% versus 37%, p = 0.009) and for incidentally detected versus suspected tumors (p = 0.009). The most common complications were urinary fistula formation (45 operations) and acute renal failure (33). Significant predisposing factors for urinary fistula formation included central tumor location (p = 0.001), tumor size greater than 4 cm. (p = 0.001), the need for major reconstruction of the collecting system (p = 0.001) and ex vivo surgery (p = 0.001). Only 1 urinary fistula required open operative repair, while the remainder resolved either spontaneously (30) or with endoscopic management (14). Significant predisposing factors for acute renal failure included a solitary kidney (p = 0.001), tumor size greater than 7 cm. (p = 0.008), greater than 50% parenchymal excision (p = 0.001), greater than 60 minutes of ischemia time (p = 0.035) and ex vivo surgery (p = 0.001). Acute renal failure resolved in 28 patients, of whom 9 required temporary dialysis, while 5 required permanent dialysis. Overall, 8 complications (3.1%) required repeat open surgery for treatment while all other complications resolved with noninterventive or endourological management. Surgical complications contributed to an adverse clinical outcome in only 7 patients (2.9%). Nephron sparing surgery can be performed safely with preservation of renal function in most patients with renal tumors.

Acute Kidney Injury↗
PubMed1994

Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies.

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.

Adult↗
PubMed1994

Alternative complement pathway activation by CD4+ T cells of HIV infected individuals: a possible role in AIDS pathogenesis.

The mechanisms by which CD4+ T cells are eliminated during HIV infection are poorly understood. We have previously shown that HIV infected cell lines activate and fix C3 via the alternative complement pathway (ACP). In the present study we examined the ability of blood lymphocytes from 40 HIV+ individuals to fix C3. A large fraction of the CD4+ T cells reacted with anti-gp120 antibodies. These cells also carried C3 fragments in vivo and could further fix C3 if exposed to human serum in vitro. C3 activation occurred via the ACP. In some cases exposure of the lymphocytes to human serum under conditions allowing ACP activation resulted in partial elimination of CD4+ T cells. The results suggest that complement activation and fixation by CD4+ T cells opsonized with HIV particles or gp120 may contribute to their selective destruction.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Characterization of tumor-infiltrating lymphocyte subsets from human renal cell carcinoma: specific reactivity defined by cytotoxicity, interferon-gamma secretion, and proliferation.

The detection of T cells with specificity for human renal cell carcinoma (RCC) has been difficult to document. In an attempt to improve our identification of RCC-reactive T cells, tumor-infiltrating lymphocytes (TIL) were expanded in interleukin-2/interleukin-4 (IL-2/IL-4) and then separated into CD4+ and CD8+ subsets using antibody-coated biomagnetic beads. TIL grown in IL-2/IL-4 expanded to greater numbers than TIL grown in IL-2 alone. From 16 patients in whom subset separation was performed, three CD4+ and three CD8+ TIL consistently had specificity for RCC that was detected by cytotoxicity, proliferation, or interferon-gamma (IFN-gamma) production. Four of the six lines were derived from the IL-2/IL-4 cultures. Two CD8+ TIL lines displayed specific lytic activity, lysing the autologous tumor but not allogeneic RCC or nonrenal tumors. Moreover, the lytic activity of these lines was blocked by anti-CD3 antibody, suggesting that tumor recognition was through the TCR/CD3 complex. Two additional TIL lines showed preferential lysis of RCC because they were cytotoxic for autologous tumor and one or more allogeneic RCC but not other tumor types. Two nonlytic CD4+ lines as well as the two CD8+ lines that were specifically lytic also produced IFN-gamma in response to the autologous tumor but not allogeneic RCC. Although these TIL lines produce IFN-gamma when stimulated with tumor alone, the addition of 5 U/ml of IL-2 significantly enhanced IFN-gamma secretion. The four TIL lines that showed specificity for RCC in terms of IFN-gamma production also had enhanced proliferation to the autologous RCC plus IL-2 but not to multiple allogeneic RCC plus IL-2. These studies demonstrate that TIL from RCC patients contain both CD4+ and CD8+ T cells that have specificity for RCC. In addition to cytotoxicity, specificity to RCC can be defined by IFN-gamma production and proliferation.

CD4-Positive T-Lymphocytes↗
PubMed1994

Alprazolam withdrawal in patients with panic disorder and generalized anxiety disorder: vulnerability and effect of carbamazepine.

OBJECTIVE: This study was designed to examine the possibility that patients with panic disorder are especially vulnerable to alprazolam withdrawal, as well as to evaluate the efficacy of carbamazepine as adjunctive treatment during alprazolam discontinuation. METHOD: After a 2-month open trial of alprazolam, 36 patients with panic disorder and 35 with generalized anxiety disorder entered a controlled discontinuation phase. Carbamazepine or placebo was added in a randomized, double-blind fashion, followed after 1 week by single-blind dose reduction of alprazolam, approximately 25% every third day. RESULTS: Fifty-two percent of the patients were able to discontinue alprazolam, but only 37% completed the study, maintaining alprazolam-free status for 4 weeks. Survival analysis revealed that among the patients receiving placebo as adjunctive therapy, panic disorder patients had a significantly greater dropout rate than patients with generalized anxiety disorder. While carbamazepine exerted no beneficial effect for patients with generalized anxiety disorder, it appeared to improve outcome in the panic disorder group. CONCLUSIONS: Results of this study indicate that panic disorder patients are more vulnerable to alprazolam withdrawal than patients with generalized anxiety disorder, and this may reflect a general diathesis of panic disorder patients to encounter more difficulty during drug withdrawal. Carbamazepine may selectively assist with alprazolam withdrawal in panic disorder patients. However, these data do not support its widespread use during benzodiazepine discontinuation, especially given its potential toxicity. In light of a proposed greater vulnerability of panic disorder patients to withdrawal, future studies need to account for differential effects related to specific diagnosis.

Adult↗
PubMed1994

Clostridium perfringens type A enterotoxin induces tissue damage and fluid accumulation in rabbit ileum.

Rabbit ileal loops were treated with purified Clostridium perfringens enterotoxin (CPE) to compare the onset of toxin-induced tissue damage with the onset of fluid transport changes (i.e. diarrhoea). Mild changes in fluid transport were detectable after 15 minutes of toxin treatment and then increased progressively with time. Histopathologic studies on toxin-treated ileal loops and measurement of toxin-treated loop fluid protein contents (an indirect marker for tissue damage) both indicated that detectable CPE-induced tissue damage also occurred within 15 minutes of toxin treatment and then progressively increased for at least the first 30 minutes of CPE treatment. Luminal fluid from CPE-treated loops contained elevated Ca2+ levels compared to control luminal fluid, but these elevated Ca2+ levels were not required to initiate in vivo CPE pathophysiologic effects. Since the onsets and severity of tissue damage and fluid transport changes coincided for at least the first 30 minutes of CPE treatment in our study, these results are consistent with CPE-induced tissue damage having a role in the initiation and extent of diarrhoea occurring during C. perfringens type A food poisoning.

Animals↗
PubMed1994

[BCG vs interferon A for prevention of recurrence of superficial bladder cancer. A prospective randomized study].

A total of 78 patients with superficial bladder carcinoma were prospectively randomized to two groups following complete transurethral resection (TUR). Each received 12 intravesical instillations of 10(7) units interferon A or 120 mg BCG Connaught for 1 year starting 6 weeks post-TUR. After a mean observation period of 24 (13-31) months in the BCG and 25 (6-32) months in the IFN group 5/32 (15.6%) recurrences in the BCG versus 21/35 (60%) in the IFN group were observed (P = 0.0003). In the IFN group 18.4% of the patients had dysuria and 2.6% fever; in the BCG group 35% had fever, 60% cystitis, 1 patient granulomatous epididimoorchitis and 1 patient pneumonitis with granulomatous prostatitis. With our instillation regimen interferon A had few side effects but also no prophylactic effect, whereas BCG had tolerable-seldom severe--side effects and was very effective in preventing recurrences. Perhaps IFN should be given earlier after TUR and in a higher dosage.

Administration, Intravesical↗