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E Klein

Publications and source records attributed to E Klein.

At least 91 records · Page 5Linked to original sources

S-methyl derivatives from thiol compounds by the pyrolytic reaction with trimethylsulfonium hydroxide.

Base-catalyzed transesterification of acyl lipids with methanol in the presence of trimethylsulfonium hydroxide (TMSH) is an easy and convenient method for the preparation of fatty acid methyl esters for gas chromatography (GC) analyses. Free fatty acids are converted to fatty acid methyl esters by the pyrolytic reaction with TMSH as well. We have found that lipids and other compounds containing thiol groups are also converted easily to the corresponding methyl sulfides (methyl thioethers) by the pyrolytic reaction with TMSH occurring in the injector of the gas chromatograph. For example, alkane thiols such as dodecane thiol and octadecane thiol are converted to the corresponding alkyl methyl sulfides, whereas bis(methylthio) derivatives are formed from alpha,omega-alkane dithiols, e.g., 1,8-octanedithiol, and from 2,3-dimercaptopropan-1-ol (dimercaprol). Furthermore, 3beta-mercaptocholest-5-ene (thiocholesterol) is converted to 3-methylthiocholest-5-ene by the same reaction. The S-methylation reactions which finally lead to the corresponding methylthio derivatives of lipids and other compounds with thiol groups may be of diagnostic value for the structural analysis of such compounds by GC and GC/mass spectrometry.

Biochemistry↗

Superficial bladder cancer: the role of interferon-alpha.

PURPOSE: We evaluate the clinical experience with recombinant interferon-alpha in superficial transitional cell carcinoma and discuss the most rational use of recombinant interferon-alpha in the context of current treatment options. MATERIALS AND METHODS: The available data were reviewed and discussed at a consensus conference in August 1996. The conclusions and recommendations are those of the authors based on the consensus reached at that meeting. RESULTS: While bacillus Calmette-Guerin (BCG) is recognized as the most efficacious intravesical agent in the prophylaxis and treatment of superficial transitional cell carcinoma, it is associated with significant toxicities and a 20 to 40% relapse rate. Interferons, particularly recombinant interferon-alpha, have demonstrated efficacy against primary and recurrent papillary transitional cell carcinoma and carcinoma in situ with minimal toxicity, although the response and relapse rates are inferior to BCG. Intravesical recombinant interferon-alpha therapy has also produced responses in patients who failed to respond or were refractory to BCG or chemotherapy. CONCLUSIONS: The clinical experience suggests that recombinant interferon-alpha has an important role in the treatment of superficial transitional cell carcinoma, particularly as second line therapy following failure of BCG or chemotherapy, and it may have synergistic effects when combined with chemotherapy or BCG. We propose a prospective randomized study comparing the efficacy of recombinant interferon-alpha, BCG and BCG plus recombinant interferon-alpha as maintenance following complete response to primary BCG therapy. The proposed study would also investigate the efficacy of BCG plus recombinant interferon-alpha as second line therapy following BCG failure. This study will be important to determine the most effective strategy to integrate recombinant interferon-alpha into current treatment options for superficial bladder cancer.

Administration, Intravesical↗

Preoperative serum hCG level and intraoperative failure of laparoscopic linear salpingostomy for ectopic pregnancy.

OBJECTIVE: To identify factors that predict failure of linear salpingostomy requiring salpingectomy for ectopic pregnancy. METHODS: Using a retrospective cohort, we examined the various risk factors of women with ectopic pregnancies presenting for conservative laparoscopic management. Success or failure of laparoscopic linear salpingostomy was the primary end point. RESULTS: One hundred fifty-seven women underwent laparoscopic linear salpingostomy for ectopic pregnancy, of whom 120 had successful procedures and 36 had unsuccessful operations because of bleeding and needed subsequent salpingectomy either by laparoscopy or laparotomy. The likelihood of success of laparoscopic linear salpingostomy was unrelated to gestational age, size of the ectopic pregnancy, surgical technique, or experience of the surgeon or resident. However, median (quartiles) serum beta hCG levels were significantly higher in patients who underwent failed salpingostomy (10,103 [3549-19,962] IU/L) compared with those who underwent successful salpingostomy (1692 [565-3971] IU/L, P < .01). Median blood loss (225 [181-562] mL versus 100 [50-200] mL, respectively, P < .01) and mean (+/- standard error of the mean [SEM]) operating times (111.1+/-6.1 minutes versus 76.8+/-2.3 minutes, P < .01) were significantly greater with failed salpingostomy followed by salpingectomy, compared with successful salpingostomy. CONCLUSION: Preoperative serum beta hCG level was the only significant determinant of failure of laparoscopic linear salpingostomy for ectopic pregnancy. Morbidity due to intraoperative blood loss and operating time was significantly increased as a result of attempting and failing to complete laparoscopic linear salpingostomy.

Adult↗

Recognition of B-CLL cells experimentally infected with EBV by autologous T lymphocytes.

We compared 5-day-old cultures of two B-CLL clones experimentally infected with EBV for their interaction with autologous T lymphocytes. The clone which was strongly activated by the virus stimulated autologous T cells. It was also damaged by the cytotoxic T cells which were generated in mixed cultures with autologous lymphoblastoid cell lines (LCL). Cultured, non-infected CLL cells were not lysed by these effectors. The other B-CLL clone, which was activated to considerably lesser extent by the virus, did not stimulate the autologous T lymphocytes. While, also in this case cytotoxic function was generated in the mixed T cell-LCL culture, the effectors did not damage the EBV-infected CLL cells. The results with B-CLL cells can be regarded as a model for the EBV genome carrier normal B lymphocytes. They substantiate the current concept that such cells persist in seropositive healthy individuals undisturbed by the specific immune response as long as they maintain the phenotype of resting cells. However, after activation they can be recognized and eliminated by T cells.

B-Lymphocytes↗

Requirement of the CD8+ or CD4+ T lymphocyte subsets for the rejection of lymphoma and fibrosarcoma grafts studied in gene knockout hosts.

Rejections of the retrovirus induced lymphomas (ALC and RBL-5) and the methylcholanthrene (MCA) induced fibrosarcoma (MC57X) grafts were tested in syngeneic CD8 and CD4 single and double knockout C57BL/6 mice. The results with the lymphomas showed that the CD8+ T cell deficiency prevented the development of rejection response induced by immunization. Deficiency of the CD4+ T subset abrogated also the rejection of ALC. Immunity against the fibrosarcoma cells developed in both type of single knockout mice, but not in the ones which lacked both CD4+ and CD8+ T cells. Thus CD8+ T cells were required for rejection of the lymphoma cells, while the CD4+ T cells only mediated a weak response. In absence of CD8+ T cells, CD4+ T cells were sufficient to reject the fibrosarcoma cells.

Animals↗

Tumor surveillance: expression of the transporter associated with antigen processing (TAP-1) in ex-vivo human tumor samples and its elevation by in vitro treatment with IFN-gamma and TNF-alpha.

We have analyzed 30 human tumor specimens (two breast, six lung, and 21 ovarian carcinomas and one malignant melanoma) for the expression of the transporter associated with antigen processing, TAP-1. Cell suspensions judged to contain negligible contamination with non-tumor cells were tested for reactivity with the antibody directed to TAP-1 in Western blot. According to these results all lysates prepared from the tumor samples contained the protein, but with considerable quantitative variations. Tumors exposed in vitro for a short time to IFN-gamma and TNF-alpha had elevated TAP-1 levels in 12 out of 30 experiments. In accordance with previous results, the tumor cell populations were heterogeneous with regard to MHC class I expression, as analyzed by indirect immunofluorescence on viable cell suspensions. Short term in vitro treatment with IFN-gamma and TNF-alpha elevated MHC class I expression in several tumors. In several mixed cultures, cytokine treated tumor cells induced cytotoxic activity in autologous or allogeneic lymphocyte populations. In vitro treatment with IFN-gamma and TNF-alpha upregulated thus the expression of MHC class I and TAP-1 in a fraction of the tumor samples. However the potentiation of the capacity to interact with T cells induced by the cytokines was not always parallel with the changes in these two parameters. It is therefore likely that the cytokine treatment induced additional changes in the tumors which contributed to their capacity to elicit the T cell response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prostate rebiopsy is a poor surrogate of treatment efficacy in localized prostate cancer.

PURPOSE: Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk. MATERIALS AND METHODS: A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status. RESULTS: Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy. CONCLUSIONS: This series demonstrates that the risk of a false-negative sextant biopsy in the presence of documented prostate cancer is high and is affected by several factors, including PSA and hormonal status. These data suggest that prostate sextant rebiopsy is an inaccurate method of assessing the therapeutic efficacy of treatments for carcinoma of the prostate in which the gland remains in situ following therapy.

Adenocarcinoma↗

Preliminary evidence for a beneficial effect of low-frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia.

OBJECTIVE: This study was designed to evaluate the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) at low-frequency in patients with major depression and schizophrenia. EXPERIMENTAL DESIGN: We investigated the therapeutic effect of a course of 10 rTMS sessions in 14 subjects with major depression (MD) and 10 with schizophrenia. PRINCIPAL OBSERVATIONS: Seven of the depressed patients reported significant improvement in depressive symptomatology, and seven of the schizophrenic subjects reported amelioration of anxiety and restlessness. CONCLUSIONS: These preliminary results suggest that low-frequency rTMS may be beneficial mainly in MD and to some extent in schizophrenia, and support the need for controlled studies to further validate its therapeutic potential.

Adult↗

Capture of anti-(Galalpha1-3Gal) antibodies by immobilized Galalpha1-3Gal oligomers derived from carrageenan.

An immobilized Galalpha1-3Gal-bearing affinity ligand was prepared as a possible prophylactic binding site of human anti-(Galalpha1-3Gal) antibodies for the prevention of hyperacute rejection of pig xenografts. lambda-Carrageenan, a natural polysaccharide known to possess alternately alpha1-3 and beta1-4-linked D-galactopyranose sulphate residues, was selectively degraded by acetolysis and subsequently deacetylated to obtain lambda-carrageenan oligosaccharides. The resulting syrup was ultrafiltered to remove higher polymers and chromatographed on Sephadex G-15 to produce a series of sized oligosaccharide fractions. An immuno-dot-blot method was established on the basis of the competition between the lambda-carrageenan oligosaccharides in solution and bovine thyroglobulin (BTG), a glycoprotein known to express the Galalpha1-3Gal marker, as the solid-phase antigen. Increasing amounts of lambda-carrageenan fractions added to normal human plasma resulted in a progressive decrease in Galalpha1-3Gal-specific human IgM and IgG binding to BTG. Complete inhibition of Galalpha1-3Gal-specific human immunoglobulin was attained at concentrations less than 0.6 mg of carbohydrate/ml of human plasma with the more active fractions. These bioactive lambda-carrageenan oligosaccharides were immobilized on hydrazide-modified microporous nylon membranes, yielding capacities between 2.18 and 2.86 mg/ml of membrane. A subsequent decrease in the human anti-(Galalpha1-3Gal) antibody level in normal human plasma was demonstrated and proved with the established immuno-dot-blot procedure.

Animals↗

[Identification of sentinel and axillary node involvement in breast cancer].

Axillary node dissection for breast cancer is important for staging and prognosis. "Sentinel nodes" are the first nodes into which primary cancer drains. Identification, removal and pathological examination of those nodes indicates whether completion of axillary lymphadenectomy is required. The sentinel nodes are identified using a vital dye injected at the primary tumor site. With this technique we were able to identify sentinel nodes in 46 of 48 (95%) women examined. An average of 2.7 +/- 1.2 nodes were identified as sentinel nodes. In 81% of cases there was a correlation between involvement of sentinel nodes and of other axillary nodes as well. In 10% of patients sentinel nodes were involved with tumor while other axillary nodes were negative. The major problem in routine application of this is relationship in surgical decisions is reliable real time pathological identification of lymph node involvement by tumor.

Adult↗

Effect of single and repeated administration of fluvoxamine on noradrenaline release in rat brain.

In vivo microdialysis in conscious rats was used to evaluate the effect of acute and chronic administration of fluvoxamine on extracellular levels of noradrenaline, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the frontal cortex. A single administration of fluvoxamine (12 mg/kg i.p.) during dialysate collection caused a significant delayed decrease in 5-HIAA and a mild increase in noradrenaline with no change in HVA and DOPAC levels. Chronic administration of fluvoxamine (12 mg/kg i.p. daily for 3 weeks, last dose 24 h prior to microdialysis) or a single dose 24 h prior to microdialysis had no effect on noradrenaline, DOPAC and HVA levels in the frontal cortex; 5-HIAA levels were significantly decreased 24 h after a single dose, but increased following long term treatment. Tissue concentrations of 5-HT and 5-HIAA in the frontal cortex showed a mild (though not significant) increase in rats chronically treated with fluvoxamine. Release of noradrenaline in the frontal cortex may be enhanced initially by a 5-HT uptake inhibitor, but this effect is not seen following drug washout.

3,4-Dihydroxyphenylacetic Acid↗

B-CLL cells with unusual properties.

In studies concerning the interaction of B-CLL cells and Epstein-Barr virus (EBV), we encountered one patient whose cells had several unusual properties. In addition to the B-cell markers, the CLL cells expressed the exclusive T-cell markers CD3 and CD8 and carried a translocation t(18,22)(q21;q11), involving the bcl-2 and Ig lambda loci. The patient represents the 4th reported CLL case with this translocation. The CLL cells could be infected and immortalized by the indigenous and by the prototype B958 virus in vitro. The T-cell markers were not detectable on the established lines. In all experiments the immortalized lines originated from the CLL cells. Their preferential emergence over virus-infected normal B cells may be coupled to the high expression of the bcl-2 gene due to the translocation. In spite of the sensitivity of CLL cells to EBV infection in vitro, no EBNA-positive cells were detected in the ex vivo population. In vitro, we could generate cytotoxic function in T-lymphocyte cultures which acted on autologous EBV-infected CLL cells. Therefore we assume that if such cells emerged in vivo they were eliminated by the T-cell response.

Aged↗

Transcranial magnetic stimulation induces alterations in brain monoamines.

Transcranial magnetic stimulation has been suggested as a possible therapeutic tool in depression. In behavioral models of depression, magnetic stimulation induced similar effects to those of electroconvulsive shock. This study demonstrates the effect of a single session of rapid TMS on tissue monoamines in rat brain. Alterations in monoamines were selective and specific in relation to brain areas and type of monoamine. The results imply on a biochemical basis to the suggested ECT-like treatment potential of TMS.

Animals↗

Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro.

We tested 20 human carcinoma samples for the production of transforming growth factor beta (TGFbeta) in vitro. Tumour cell suspensions without obvious contamination with non-malignant cells were kept in culture conditions for 16 h and their supernatants were added to CCL-64 cells. The proliferation of these cells is inhibited by TGFbeta. According to this assay, the supernatants contained both active and latent TGFbeta. In addition, the supernatants were found to suppress the spontaneous cytotoxic function and activation of T-cell-enriched lymphocyte populations. A specific monoclonal antibody (mAb) counteracted these effects and therefore we concluded that they were mediated to a large extent by TGFbeta. In line with the results obtained with the supernatants, activation of lymphocytes could also be inhibited by tumour cells and their inhibitory effect was weaker in the presence of the TGFbeta-specific mAb. It is important to note that, when TGFbeta-specific mAb was added to autologous mixed lymphocyte/tumour cell cultures, lymphocyte activation occurred more often. These results thus substantiate the assumption that production of TGFbeta may help the survival of potentially immunogenic tumour cells in immunocompetent patients.

Carcinoma↗

Transitional cell carcinoma in situ of the seminal vesicles: 8 cases with discussion of pathogenesis, and clinical and biological implications.

PURPOSE: Mucosal migration of transitional cell carcinoma in situ is a potential mechanism for multifocal lower tract disease. MATERIALS AND METHODS: The clinical course and pathological studies of 8 cases of carcinoma in situ are reviewed in detail. RESULTS: The pattern of disease of carcinoma in situ of seminal vesicle provides circumstantial evidence for mucosal migration of cancer from a bladder or prostatic urethral origin. CONCLUSIONS: A monoclonal origin of bladder cancer combined with mucosal spread of carcinoma in situ suggests that incomplete destruction of carcinoma in situ may adversely affect long-term results by permitting extension into the distal ureters, prostatic duct or seminal vesicles. Protracted intravesical treatment of carcinoma in situ without complete elimination of the disease allows the natural history of mucosal spread to become evident.

Aged↗

PSA levels and the rate of positive surgical margins in radical prostatectomy specimens preceded by androgen blockade in clinical B2 (T2bNxMo) prostate cancer. The Lupron Depot Neoadjuvant Study Group.

OBJECTIVES: Neoadjuvant hormonal therapy reduces positive margins in patients undergoing radical prostatectomy. All patients experience a decrease in serum prostate specific antigen (PSA), but not always to a level that is nondetectable. The results of several prospective, randomized trials indicate that the incidence of positive margins decreases with the use of androgen deprivation prior to radical prostatectomy. It has been suggested that a greater decline in PSA levels would result in fewer positive margins. In a recent US trial of patients with T2bNxMO prostate cancer, we reported that 18% of patients randomized to receive 3 months of leuprolide acetate and flutamide had positive margins, compared to 48% of those who had radical prostatectomy alone (P < 0.001). We correlated the PSA levels prior to and following androgen deprivation and the presence of a positive margin following radical prostatectomy (RP). METHODS: One hundred and thirty-seven of 149 patients randomized to receive presurgery androgen deprivation (AD) underwent radical prostatectomy. Of these, 135 had a PSA level obtained both prior to androgen deprivation and prior to surgery. We analyzed the percent positive margins in patients whose PSA values became undetectable and in those whose values remained above 0.1 ng/mL despite androgen deprivation. RESULTS: Eight of 43 patients (19%) with a nadir PSA < or = 0.1 ng/mL had a positive surgical margin and 16/92 (17%) with a nadir PSA > 0.1 ng/mL had tumor at the margin. There were no statistical differences in these two groups (P = 1.0 by Fisher's Exact Test [two-tailed], and the Pearson correlation was -0.015). CONCLUSIONS: There was no correlation between an undetectable PSA and a PSA > 0.1 ng/mL and the presence of tumor at the margin when 3 months of AD was given prior to RP. It is possible that longer periods of AD prior to RP will reduce PSA to an undetectable level in a higher percent of patients. However, these data suggest that an undetectable level will not result in less positive margins.

Aged↗

Decreasing striatal 6-FDOPA uptake with increasing duration of cocaine withdrawal.

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects. Middle abstinence cocaine addicts (n = 5, off cocaine 11-30 days) had significantly lower striatal 6-FDOPA uptake compared to normal controls or early abstinence cocaine addicts (n = 6, off cocaine 1-10 days). The cocaine-dependent subjects (n = 11) showed a significant negative correlation between days off cocaine and striatal 6-FDOPA uptake. The results suggest that during abstinence from cocaine there is a delayed decrease in dopamine terminal activity in the striatum.

Adult↗