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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 181 records · Page 10Linked to original sources
PubMed1993

The effect of surgical intervention for head and neck cancer on whole salivary flow: a pilot study.

For many patients, rehabilitation and quality of life after treatment of head and neck cancer are issues that confront both them and their physicians. Various levels of xerostomia are often reported as one of the side effects of treatment. This study evaluated the effects of surgical intervention (alone) that involve major salivary glands on whole salivary flow. Five subjects with head and neck cancer who lost a submandibular gland at surgery were evaluated before and after treatment to determine resting and stimulated whole salivary flow rates. Three subjects demonstrated a decrease in resting and three a decrease in stimulated flow rates compared with pretreatment levels. Two subjects rebounded to near or above presurgery flow rates. Although a trend was identified for a decrease in resting and stimulated flow rates, the sample size was too small to statistically validate this trend. The decreases in flow rates recorded at the last test were of insufficient magnitude to elicit a complaint of xerostomia.

Aged↗
PubMed1993

Overall interleukin-6 production exceeds 7 mg/day in multiple myeloma complicated by sepsis.

We previously reported that injection of anti-IL-6 monoclonal antibody (mAb) in a patient with multiple myeloma (MM) induced the circulation of high amounts of IL-6 in the form of IL-6/anti-IL-6 monomeric complexes. This made it possible to estimate overall daily IL-6 production in patients in vivo, which had not been achieved in animals or humans before. In this study, estimations are given for a patient with MM who developed Escherichia coli sepsis during anti-IL-6 mAb. During the first 12 days, the overall IL-6 production was estimated at 1.5 to 2.0 micrograms/day. On day 13, serum IL-6 concentration, in the form of IL-6/anti-IL-6 complexes, increased 1000-fold and was 1.7 x 10(6) pg/ml, in relation with the development of E. coli sepsis. Overall IL-6 production was estimated to be greater than 7 mg/day, i.e. 3500 times higher than before sepsis. Serum IL-6 levels in the form of monomeric immune complexes remained very high for 20 days after sepsis indicating the persistence of very high overall IL-6 production (100 to 3500-fold greater than pre-sepsis production). This study demonstrates a considerable and persistent potential for IL-6 production in this patient during and after sepsis.

Antibodies, Monoclonal↗
PubMed1993

Cytokine gene expression in human multiple myeloma.

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.

Blotting, Northern↗
PubMed1993

The treatment of advanced Merkel cell carcinoma. A multimodality chemotherapy and radiation therapy treatment approach.

BACKGROUND: The optimal management of Merkel cell carcinoma has not been clearly defined. OBJECTIVE: To describe the treatment of eight patients who presented with Merkel cell carcinoma. METHODS: Eight patients with advanced locoregional Merkel cell carcinoma were seen in our institute over a 7-year period. Four patients were successfully treated by induction chemotherapy after excisional biopsy, followed by radiotherapy. Three patients died from widespread metastases and one from neutropenic sepsis induced by chemotherapy. RESULTS: These cases demonstrate the potential lethality and aggressive nature of this rare skin tumor despite its chemosensitive and radioresponsive character. In all four patients who are alive and disease-free, chemotherapy was given first and radiotherapy was given as consolidation. CONCLUSION: We suggest that a multimodality treatment approach--chemotherapy followed by radiotherapy--is indicated in patients with advanced Merkel cell carcinoma.

Adult↗
PubMed1993

Analysis of the B-cell compartment in plasma cell leukemia and multiple myeloma: immunoglobulin gene rearrangement of EBV-infected B-cell lines.

Multiple myeloma (MM) is defined as a tumoral expansion of plasma cells occurring in the bone marrow and sometimes in the peripheral blood (plasma-cell leukemia, PCL). Many reports have demonstrated a clonal expansion of B cells bearing the same idiotypic determinants as the myeloma protein (idiotypic B cells) in MM, suggesting that they could belong to the malignant clone. In order to investigate whether the B-cell population is a malignant component or not, either in the peripheral blood of patients with PCL or in the bone marrow of patients with MM, we derived B-cell lines by infecting, with the Epstein-Barr virus (EBV), cultures in limiting dilution of mononuclear cells from six patients. A limiting dilution culture was used to prevent the elimination of slowly proliferating clones by the more rapidly dividing ones, and thus to get the most exact representation of the B-cell repertoire of these patients. The cloning efficiency of the EBV-infected cells was similar in patients and healthy individuals (range: 1 in 100 to 1 in 1650 B cells). All of the clones obtained from a single patient exhibited different clonal immunoglobulin gene rearrangements (IGR), proving the validity of our cloning technique. No tumoral clones (61 clones analysed) showed the IGR pattern specific of autologous myeloma cells. These results indicate that malignant plasma cells cannot be immortalized with EBV. These results show that, if malignant B cells (pre-switch or post-switch) exist, they could be present only in a minor population, and the corollary of this is that there is a major population of non-malignant B cells in the sites of tumoral proliferation of patients with MM. This is remarkable in view of numerous reports showing a profound defect of the polyclonal B lymphopoiesis in these patients, and even an absence of B lymphocytes. Thus, these results challenge the existence of a major compartment of malignant idiotypic B cells and favor the hypothesis of non-malignant B cells sharing cross-reactive idiotypes with the autologous myeloma protein.

Antigens, CD↗
PubMed1992

C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system.

Multiple myeloma (MM) staging procedures are still inadequate for detection of the optimal therapeutic procedure for an individual patient. The Durie & Salmon staging system and serum beta 2-microglobulin (beta 2M) are used worldwide because of their easy clinical application. Other prognostic parameters, such as myeloma cell proliferative activity, are of exceeding importance, but are not as simple as standard methods. Recently, interleukin-6 (IL-6) has been shown to be a major growth factor for MM. IL-6 is a pleiotropic cytokine acting on several cell lineages, and, at the hepatocyte level, stimulates the synthesis of acute phase proteins, such as the well known C-Reactive Protein (CRP). Serum CRP concentration actually reflects the IL-6 activity. A survival analysis carried out in 162 MM patients at diagnosis showed that serum CRP level is a highly significant prognostic factor. Moreover, serum CRP was independent of serum beta 2M. This feature allowed stratification of MM patients into 3 groups according to CRP and beta 2M serum levels: (1) low risk group, CRP and beta 2M less than 6 mg/L (50% of patients); (2) intermediate risk group, CRP or beta 2M greater than or equal to 6 mg/L (35% of patients); (3) high risk group, CRP and beta 2M greater than or equal to 6 mg/L (15% of patients). Survival was 54, 27, and 6 months, respectively (P less than .0001). We thus propose a new and powerful myeloma staging system based on simple and reliable laboratory evaluations.

C-Reactive Protein↗
PubMed1992

Up-regulation of interleukin (IL)-6 receptor gene expression in vitro and in vivo in IL-6 deprived myeloma cells.

Myeloma cells absolutely require interleukin-6 (IL-6) for growing in vivo in patients with multiple myeloma and exogenous IL-6-dependent myeloma cell lines have been reproducibly obtained. In this study we show a dramatic up-regulation of the IL-6 receptor (gp80 chain) gene expression in myeloma cell lines following the removal of exogenous IL-6. Such a regulation was also known to occur in IL-6-deprived myeloma cells in vivo in three patients who were treated with optimal doses of anti-IL-6 monoclonal antibodies. The direct effect of IL-6 on IL-6 receptor gene expression in myeloma cells was further confirmed by adding IL-6 to an autonomously growing myeloma cell line.

Blotting, Northern↗
PubMed1992

Interleukin-6 dependence of advanced malignant plasma cell dyscrasias.

The authors, and others, clearly have established that interleukin-6 (IL-6) is the major growth factor for human myeloma cells in vitro. It is a critical conceptual point whether or not IL-6 remains involved in the final phases of disease progression in malignant plasma cell dyscrasias. To answer this question, the authors evaluated the in vitro IL-6 dependence of the proliferation of myeloma cells from the bone marrow of 13 patients with advanced multiple myeloma (MM) and from the peripheral blood of 13 patients with plasma cell leukemia (seven primary and six secondary cases). Their results show that myeloma cell growth was totally dependent on IL-6 in 25 of 26 patients. Myeloma cells of only one patient did not respond to IL-6 in vitro. Actually, the cells from this patient were not proliferating in vivo. Identical patterns of IL-6 dependence of myeloma cells were found in the peripheral blood and bone marrow from four patients with PCL. The authors conclude that, in the terminal phase of malignant plasma cell dyscrasias, tumoral growth is totally dependent on IL-6 in vitro. This observation is critical in considering the investigation of anti-IL-6 therapy in patients with advanced MM.

Aged↗
PubMed1992

CD5 B lymphocyte antigen in monoclonal gammopathy.

Because B lymphocytes bearing the CD5 antigen have been involved in many B-cell malignancies, we have investigated the presence of the CD5 B-cell antigen on B and plasma cells in monoclonal gammopathy. Quantification of CD5 B cells was made in the peripheral blood of seven individuals with monoclonal gammopathy of undetermined significance (MGUS) and in that of 21 patients with multiple myeloma (MM). The bone marrow of ten patients with MM was also studied. Patients with progressive MM presented a significant reduction in both B and CD5 B lymphocytes (i.e., percentages and absolute numbers), when compared with individuals with MGUS and patients with stable MM. These latter individuals and patients did not differ from healthy donors. No CD5 B cells were found in the bone marrow of patients with MM. Moreover, no CD5 antigen could be detected on eight freshly established human myeloma cells lines including six totally dependent on interleukin-6. However, it was weakly expressed on two standard myeloma cell lines not requiring exogenous interleukin-6 (i.e., RPMI 8226 and U 266). In conclusion, our data show mainly an overall reduction of the polyclonal CD5 B lymphocytes similar to what is observed for the other polyclonal B lymphocytes in patients with active MM. Finally, the expression of the CD5 antigen human myeloma cell lines is not constant.

Antigens, CD↗
PubMed1992

High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo.

A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A-Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.

Antibodies, Monoclonal↗
PubMed1992

Isolation and characterization of a cDNA from Cuphea lanceolata encoding a beta-ketoacyl-ACP reductase.

A cDNA encoding beta-ketoacyl-ACP reductase (EC 1.1.1.100), an integral part of the fatty acid synthase type II, was cloned from Cuphea lanceolata. This cDNA of 1276 bp codes for a polypeptide of 320 amino acids with 63 N-terminal residues presumably representing a transit peptide and 257 residues corresponding to the mature protein of 27 kDa. The encoded protein shows strong homology with the amino-terminal sequence and two tryptic peptides from avocado mesocarp beta-ketoacyl-ACP reductase, and its total amino acid composition is highly similar to those of the beta-ketoacyl-ACP reductases of avocado and spinach. Amino acid sequence homologies to polyketide synthase, beta-ketoreductases and short-chain alcohol dehydrogenases are discussed. An engineered fusion protein lacking most of the transit peptide, which was produced in Escherichia coli, was isolated and proved to possess beta-ketoacyl-ACP reductase activity. Hybridization studies revealed that in C. lanceolata beta-ketoacyl-ACP reductase is encoded by a small family of at least two genes and that members of this family are expressed in roots, leaves, flowers and seeds.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗
PubMed1992

Prognostic factors in node-positive operable breast cancer patients receiving adjuvant chemotherapy.

A retrospective analysis of prognostic factors in 214 consecutive node-positive (N+) operable breast cancer patients, receiving Melphalan + 5-fluorouracil adjuvant chemotherapy between 1980 and 1984 was performed. Median follow-up was 95 months. Actuarial disease-free interval (DFI) and survival (S) were determined according to age, menopausal status, histology, size of primary tumor (T), multifocality, tumor location, hormonal receptor status, number of N+, size of N+, tumor spread in axillary fat, and interval between surgery and onset of adjuvant chemotherapy. On univariate analysis two factors were prognostic for DFI and S: number of N+ and T size. A comparison between traditionally classified T1 and T2 patients revealed no significant difference, but when the cut-off point was shifted from 2 cm to 3 cm, T size represented a highly significant prognostic factor. In patients with T less than or equal to 3 cm 5-year DFI was 54% and 5-year S was 76%, while in patients with T greater than 3 cm the respective values were 23% (p less than 0.001) and 41% (p less than 0.001). These significant DFI and S differences persisted after adjustment for number of N+ by bivariate analysis. Multivariate analysis supported the importance of T greater than 3 cm as a strong adverse predictor. Four adverse variables, T greater than 3 cm, number of N+ greater than or equal to 4, multifocality, and tumor spread in axillary fat were used to divide our patients into three subsets with significantly different DFI: Group I, with none of the above factors; Group II, with only one factor present; and Group III, with more than one factor present (5 years DFI 66%, 45%, and 21%, respectively; p less than 0.001).

Breast Neoplasms↗
PubMed1992

The critical role of interleukin-6, interleukin-1B and macrophage colony-stimulating factor in the pathogenesis of bone lesions in multiple myeloma.

Lytic bone lesions and hypercalcemia are common features of multiple myeloma. In contrast, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating increased osteoclastic resorption with decreased bone formation. Several osteoclast-activating factors, such as interleukin-1, macrophage colony-stimulating factor, and interleukin-6, are involved in this process. However, interleukin-6, the major myeloma cell growth factor, plays a critical role in myeloma-induced bone resorption.

Bone Resorption↗