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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 217 records · Page 12Linked to original sources
PubMed1991

Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia.

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.

Acute-Phase Proteins↗
PubMed1991

No expansion of the pre-B and B-cell compartments in the bone marrow of patients with multiple myeloma.

We have recently demonstrated that the CD24 antigen density of bone marrow (BM) lymphoid cells discriminates between pre-B cells and mature B-cells. Using this new method, we evaluated the B-cell lineage in the BM and peripheral blood (PB) of 18 patients with multiple myeloma (MM). First, the percentage of pre-B cells was significantly reduced by 40% in the BM of patients with MM: 2.3% +/- 2.2% versus 5.7% +/- 2.8% of normal BM lymphoid cells (P less than 0.01). This finding was associated with a significant reduction (50%) of the percentage of mature B-cells in both BM and PB, especially in patients with progressive disease (P less than 0.05). In contrast to what has been reported previously, we have not found any pre-B cells in the PB of these patients with MM. Secondly, BM pre-B and B-cell patients with MM did not express any activation markers (CD23, CD25, or CD71 antigens) and no CD5+ B-cells were found in the BM unlike in PB (8% CD5+ B-cells). Taken together, these data do not support the concept of a direct involvement (i.e, expansion or activation) of pre-B cells in MM without excluding the possibility of an early oncogenic event at the pre-B cell stage. Furthermore, our data emphasize this important reduction of the B-cell compartment (including that of pre-B cell) as a major cause of the humoral immunodeficiency in MM.

Antibodies, Monoclonal↗
PubMed1991

Soluble histocompatibility antigen class I in breast cancer patients in relation to tumor burden.

Serum beta-2 microglobulin (B-2M) levels were studied in 365 breast cancer patients and 210 age-matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow-up; and Group C, metastatic patients. The mean B-2M of all breast cancer patients plus or minus one standard deviation (3.5 +/- 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 +/- 0.49; range, 0.3 to 2.3; P less than 0.005). When the three patient groups were compared with each other, the mean B-2M level of Group A (3.0 +/- 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 +/- 1.1; range, 2.0 to 6.4). The mean B-2M of both Groups A and C was significantly higher than that of Group B (2.38 +/- 1.02, range, 0.4 to 5.4; P less than 0.001). In Group A the mean B-2M decreased significantly after a 12-month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B-2M levels between Stages I and III. In relapsing patients, mean B-2M levels increased. These findings suggest that serum B-2M levels may reflect tumor burden, and even in patients at follow-up, occult tumor cells may activate the immune system.

Adult↗
PubMed1991

Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication.

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in the megakaryocytic differentiation. Recently, we have observed that IL-6 is synthesized by several human cell lines with megakaryocytic features. In this study, we have investigated whether a similar phenomenon occurs during normal megakaryocytic differentiation. Human megakaryocytes (MK) were obtained by culturing normal marrow in liquid culture with aplastic plasma (AP). First, an IL-6 secretion in bone marrow culture enriched in MK as well as in purified MK populations was demonstrated by a biologic assay. Second, IL-6 mRNA was detected in a purified population of MK by the polymerase chain reaction and dot blot analysis. IL-6 mRNA and protein were undetectable in platelets. Third, in situ hybridization procedure demonstrated the presence of IL-6 mRNA in individual immature MK. Fourth, IL-6 protein was detected in MK at the unicellular level by an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6. Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in situ hybridization using an IL-6-R probe and in situ autoradiography after binding with [125I]-labeled recombinant IL-6. The IL-6 endogenously produced in liquid cultures containing normal human plasma or AP was subsequently neutralized. This resulted in a 50% decrease of the MK growth with a minor shift in the ploidy distribution toward lower values. In semisolid cultures the addition of anti-IL-6 antibodies led to a 42% decrease in colony number in cultures stimulated by IL-3 but not in other conditions of culture. These results suggest that normal human megakaryocytopoiesis might be regulated in part by an IL-6 autocrine loop.

Antibodies, Monoclonal↗
PubMed1991

Prospective analysis of masticatory function following lateral mandibulotomy.

Based on clinical impressions and subjective reports by patients, it is generally accepted that a loss of mandibular continuity will result in decreased masticatory function while preserving continuity will result in maintenance of masticatory function. Surprisingly, there is a paucity of well controlled studies objectively evaluating masticatory function to support these statements. The purpose of this study was to objectively evaluate masticatory function in a patient who underwent surgical resection for cure of a tonsillar carcinoma where a lateral mandibulotomy was used. Masticatory performance and swallowing threshold were assessed using a 0.5 gm frito as the test food substance and a sieve analysis. The subject was evaluated pre and post surgery and post prosthetic rehabilitation. When compared with pre surgery function, masticatory function and swallowing threshold were maintained and enhanced with prosthetic treatment 1 year post surgery. Maintenance of mandibular continuity did have functional merit for the subject studied.

Denture, Complete, Upper↗
PubMed1991

The effect of head and neck cancer treatment on whole salivary flow.

The effects of multimodality therapy for head and neck cancer on whole salivary flow were evaluated. Eighteen subjects with head and neck cancer were studied. Resting and stimulated whole salivary flow rates were recorded, pretreatment, after individual modality therapy, and posttreatment. Twenty-four subjects with no history of head and neck cancer matched for age, and sex distribution, served as controls. Primary site, stage, major salivary glands resected, radiation fields, and dose to major salivary glands are reported. The average salivary flow rates for 18 subjects following treatment was reduced 83% for resting and 86% for stimulated saliva from pretreatment levels. The null hypothesis that the overall resting and stimulated whole salivary flow rates are unaffected by treatment (surgery and radiation) of the head and neck cancer was rejected (P values at 0.05 level of significance). Stage and location of primary, total dose delivered to and volume of gland exposure are important factors when predicting xerostomia following multimodality therapy.

Adult↗
PubMed1991

Human recombinant dimeric IL-6 binds to its receptor as detected by anti-IL-6 monoclonal antibodies.

Three different epitopes of the human IL-6 (IL-6) molecule were recognized by the mAb B-E4 (IgG2b), B-E8 (IgG1) and B-F6 (IgG1). The affinities of these three mAb for IL-6 differ little in several assays but if ranked by affinity they fall into the following order B-E8 greater than B-E4 greater than B-F6. B-E4 and B-E8 mAb, recognizing two different epitopes, are inhibiting mAb in the bioassay with the IL-6 depending cell line B9, however B-E8 has an inhibiting activity higher than B-E4. Both human natural IL-6 (HnIL-6) and human recombinant IL-6 (HrIL-6) were inhibited but not the murine natural IL-6 (MnIL-6). Surprisingly, not only the non-inhibiting mAb (B-F6) recognizes the HrIL-6 fixed to the receptor but also the inhibiting mAb B-E4 and B-E8. This together with the results obtained in a sandwich ELISA where the same mAb was used as both catcher and tracer to detect HrIL-6, it was concluded that dimeric HrIL-6 is able to fix the IL-6 receptor. Competition studies between monomeric HnIL-6 and dimeric HrIL-6 showed that the affinity of the dimeric HrIL-6 for the receptor was higher than that of HnIL-6.

Animals↗
PubMed1991

Expression of HLA class I and class II in gastric carcinoma in relation to pathologic stage.

The expression of HLA class I and II antigens was studied in 41 patients with gastric cancer and in 2 normal stomachs. The normal gastric epithelia were diffusely stained for class I antigens. No staining was observed for class II. In gastric cancer an overall reduction in staining was observed, which was related to the degree of tumor penetration through the gastric wall. In tumors which penetrated the mucosa and submucosa only, 80-90% of tumor cells were stained for class I, as well as the normal areas surrounding the tumor. On the other hand, in tumors which penetrated through the organ to the fat, only 10-20% of cells were stained. Staining for class II was observed in only 12 cases, all of them advanced, with penetration to muscle or fat. No staining was observed in the normal areas surrounding the tumor. The importance of HLA antigens in immune surveillance is discussed.

Gastric Mucosa↗
PubMed1991

Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro.

Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection.

Adjuvants, Immunologic↗
PubMed1991

Cellular B-2 microglobulin expression as a prognostic indicator in renal cell carcinoma.

The expression of B-2 microglobulin (B-2M) on tumor cells and their normal cell counterparts in 39 patients with renal cell carcinoma was studied and correlated to tumor stage and survival. The median survival time of patients with localized disease (stage I) whose tumors expressed B-2M was 10.2 years while the median survival time for patients whose tumors did not express B-2M was only 3.6 years (p less than 0.001). For patients with more advanced disease (stages II, III, IV) whose tumors expressed B-2M, median survival time was 3.6 years compared to 2.0 years in patients whose tumors did not express B-2M, a non-significant difference. It is suggested that the tumor cell membrane expression of B-2M may serve as an indicator of good prognosis in early renal cell carcinoma.

Adolescent↗
PubMed1991

Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.

A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, was shown to potentiate long-term cultures of mouse bone marrow stromal cells in vitro and therefore constitutes a potential tool for immortalizing such cells. Moreover, when tested in an in vitro differentiation assay, stromal cells constitutively expressing c-fos favor the granulocyte differentiation of hematopoietic precursors. Interestingly, retroviruses expressing v-src and v-abl oncogenes, included as controls in our experiments, do not produce any detectable effects, whereas those expressing polyoma virus middle T antigen facilitate long-term growth in vitro of stromal cells that favor the macrophage differentiation pathway of bone marrow stem cells. Our observation supports the idea that constitutive expression of some oncogenes, including c-fos and polyoma virus middle T antigen, may influence cytokine production by bone marrow stromal cells.

Animals↗
PubMed1991

Hairy cell transformation of a B-cell chronic lymphocytic leukemia: a morphological, cytochemical, phenotypic and molecular study.

The normal counterparts of the B cells found in hairy cell leukemia (HCL) are not known. We report here a detailed morphological, cytochemical, immunological and molecular analysis of a patient with B-cell chronic lymphocytic leukemia (B-CLL) who later in the course of his disease developed hairy cell leukemia. We speculate that hairy cell transformation of B-CLL might be related to an in vivo protein kinase C mediated cellular activation of B-CLL cells.

Blotting, Southern↗
PubMed1991

Effect of anthracycline drugs on the element content of cultured embryonic rat cardiomyocytes.

The effect of two anthracyclines--doxorubicin hydrochloride (adriamycin, CAS-25316-40-9), and 4'-epidoxorubicin (epirubicin, CAS-56420-45-2), and an anthracenedione, mitoxantrone (CAS-70476-82-3) on the element content of cultured embryonic rat cardiomyocytes was examined by X-ray microanalysis. Adriamycin induced an increase in Ca, P and S, and a decrease in Cl content. Novantrone caused a marked increase in the Na and a decrease in the Cl content, whereas epirubicin did not affect the content of any of the elements examined. In an attempt to prevent the effect of the drugs on the element content of the cells, the cardiomyocytes were incubated with a blocker of the slow Ca channels--verapamil-- and with each of the three drugs. Verapamil only induced an increase in the Ca and a decrease in the S content of the cells. Except for some protective effect on the element content of the cardiomyocytes, which was altered by adriamycin, the results did not indicate any beneficial effect of verapamil added to the other two drugs, as for this aspect of the study.

Animals↗
PubMed1991

Immunohistochemical detection of renal carbonic anhydrase of patients with recurrent urolithiasis.

In renal exploratory excisions the isoenzyme C of the carbonic anhydrase was detected in 51 operative treated patients with recurrent urolithiasis and in 6 patients with ren mobilis or stenosis of the ureteral pelvic junction by using the immunohistochemical PAP-method. In the distal tubules and collecting ducts there is an alternating occurrence of cells with small and those with strong reactivity. This correlates with the distribution of mean or principal (P-, small reaction) and intercalated (I-, strong reaction) cells. The number of carbonic anhydrase rich cells and the degree of their cytoplasmic reaction to this enzyme seem to correlate with the ability of the urine to acidify. The patients were divided into four groups according to the mean urine pH estimated for a period of two weeks. The third group with predominantly acid urine (pH less than 5.8) showed a significantly increased number of carbonic anhydrase rich cells (mean = 63% +/- 6, n = 18) as compared to the first group (controls) without urolithiasis and normal urine (pH 5.8-6.8, mean = 46% +/- 8, n = 6) or the second group with urolithiasis and normal urine (pH 5.8-6.8, mean = 46% +/- 8, n = 28). The fourth group with predominant alkaline urine (pH greater than 6.8) showed a significantly decreased number of intercalated cells (mean = 42% +/- 16, n = 5) in comparison to the third group. Indeed, the difference with the control group is not significant but the cytoplasmic reaction of I-cells decreases distinctly in comparison to all other groups.

Biopsy↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells.

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM. In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells. This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures. In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients. Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL-6 responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone. Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro.

Aged↗