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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 55 records · Page 3Linked to original sources
PubMed2000

A comparison of two dose regimens in pancreatic cancer.

Forty-seven patients with pancreatic cancer were treated with two different schedules of 5-fluorouracil (5FU) and leucovorin (LCV): standard and dose-intense schedules. The standard regimen was monthly and the dose intense was biweekly. Partial response was observed in one patient (4%), no change in 12 (48%) and progression of disease in another 12 patients. Clinical benefit, measured by symptomatic improvement, was observed in 19% of all the patients, in 12% of those treated with the standard regimen and in 27% of the intense group. Median survival was 8 months for all the patients. The 1-year survival rate was 32%. Toxicity was mild. There was no survival benefit for the dose intense regimen. These results indicate that clinical benefit can be obtained with 5FU and LCV regimens despite the lack of objective response and that a dose-intense schedule is of little benefit in treating pancreatic cancer.

Adult↗
PubMed2000

Cerebello-olivary and lateral (accessory) cuneate degeneration in a juvenile American Miniature horse.

A 12-month-old American Miniature horse colt was presented to the Virginia Tech Veterinary Teaching Hospital with a 7-month history of progressive ataxia. Physical examination revealed a head intention tremor, base-wide stance, and ataxia. Necropsy findings were confined to the brain. There were bilateral areas of liquefactive necrosis and cavitation corresponding to the dorsal accessory olivary and lateral (accessory) cuneate nuclei. Cerebellar folia of the dorsal vermis were thin. Microscopically, the cerebellar cortex was characterized by patchy areas of Purkinje cell loss with associated variable thinning of the molecular and granule cell layers and astrogliosis. Dorsal accessory olivary and lateral cuneate nuclei were cavitated and had mild glial response around their periphery. Additionally, a focus of necrosis and neuropil vacuolization was found in the right putamen. These findings indicate the presence of a neurodegenerative disorder centered, but not confined to, the cerebellum and its connections in this American Miniature horse colt.

Animals↗
PubMed2000

Analysis of the inter- and intravillous placental blood circulation in high-risk pregnancies before and after the hemodilution therapy using the colour-angio-mode.

OBJECTIVE: The aim of the study was to examine the efficiency of a hemodilution (HD) therapy on the inter- and intravillous placental blood circulation in high-risk pregnancies by applying the colour-angio-mode (CAM). PATIENTS AND METHODS: 24 patients were examined who had fetal growth retardation and/or pathological Doppler results. In all cases the hematocrit was >36%. The patients were given 500 ml Ringer solution and 500 ml HAES 10% intravenously per day; maternal heart rate and blood pressure were measured continuously. Prior to and after the therapy the same area of the placenta was examined using CAM; histograms demonstrating the distribution of the intensity values and summation values of the color pixels were calculated. RESULTS: In 14 patients the fetal outcome was good. The histograms showed in 11/14 cases an increase of low intensity values indicating an improvement of the placental circulation. The summation value of the color pixels as measured by CAM was significantly increased after the therapy in these cases (p = 0.022). In 10 patients the fetal outcome was unfavorable. The histograms showed a decrease of the intensity values in 6/10 cases. There was no significant change in the summation values of the color pixels after the therapy (p = 0.139). CONCLUSIONS: CAM sonography demonstrated for the first time a local effect of the HD therapy within the placenta. In the positive case the placental blood circulation will improve and the pregnancy develops favourably (responder). In the negative case there is no change of the placental blood circulation and pregnancy must be terminated due to a pathological fetal heart rate tracing, fetal growth failure or hypertensive disorders (nonresponder).

Adolescent↗
PubMed2000

[The expression, secretion and regulation of membrane-soluble syndecan-1 in human multiple myeloma cells].

OBJECTIVE: To analyze the expression, secretion and regulation of membrane-soluble syndecan-1 in human multiple myeloma cells, and to explore the relationship between syndecan-1 and the development of human multiple myeloma. METHODS: Syndecan-1 expression on the surface of malignant plasma cells was analyzed by immuno-staining, the levels of soluble syndecan-1 in the supernatant of cultured tumor cells by ELISA. RESULTS: 1. Human multiple myeloma cells expressed high levels of syndecan-1. The density of syndecan-1 varied from 170,000 to 800,000 molecules per cell. The expression of syndecan-1 lost rapidly as the cells underwent apoptosis. 2. Most myeloma cells produced soluble syndecan-1, the rate of production did not correlate with the density of membrane syndecan-1. Moreover, the production of soluble syndecan-1 did not require serum. 3. The protein synthesis inhibitor cycloheximide inhibited the production of syndecan-1. The serine protease inhibitor antipain did not affect the secretion of syndecan-1. CONCLUSION: As a receptor of many growth factors, cytokines and heparin-like growth factors, syndecan-1 might play an important role in tumor cell growth and homing in multiple myeloma development.

Humans↗
PubMed1999

Induced expression of B7-1 on myeloma cells following retroviral gene transfer results in tumor-specific recognition by cytotoxic T cells.

The aim of this study was to evaluate whether tumor cells from patients with multiple myeloma activate allogeneic and autologous T cells. Results showed that myeloma cells expressed few B7-2 and no B7-1 in six cell lines and primary cells from 11 patients. They expressed substantial levels of HLA class I, CD40, and a set of adhesion molecules. In accordance with the low density of B7 molecules on these cells, they were poor allogeneic CD8+ T cell stimulators. Neither IFN-gamma plus TNF-alpha nor CD40 stimulation significantly induced B7-1 or up-regulated B7-2 on human myeloma cell line or primary myeloma cells from six of seven patients. However, such induction was found on autologous bone-marrow nontumoral cells and on autologous dendritic cells following CD40 stimulation. High B7-1 expression was stably obtained on human myeloma cell line using transduction with a B7-1 retrovirus, enabling these cells to stimulate allogeneic CD8+, though not CD4+, T cell proliferation. For one patient with advanced disease, B7-1 gene transfer made it possible to amplify autologous cytotoxic T cells that killed autologous myeloma cells in an HLA class I-restricted manner, but not autologous PHA blasts. These results suggest that B7-1 gene transfer could be a promising immunotherapeutic approach in multiple myeloma.

Aged↗
PubMed1999

Immortalization and characterization of Nijmegen Breakage syndrome fibroblasts.

Nijmegen Breakage Syndrome (NBS) is a very rare autosomal recessive chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency and a high incidence of malignancies. Cells from NBS patients are hypersensitive to ionizing radiation (IR) and display radioresistant DNA synthesis (RDS). NBS is caused by mutations in the NBS1 gene on chromosome 8q21 encoding a protein called nibrin. This protein is a component of the hMre11/hRad50 protein complex, suggesting a defect in DNA double-strand break (DSB) repair and/or cell cycle checkpoint function in NBS cells. We established SV40 transformed, immortal NBS fibroblasts, from primary cells derived from a Polish patient, carrying the common founder mutation 657del5. Immortalized NBS cells, like primary cells, are X-ray sensitive (2-fold) and display RDS following IR. They show an increased sensitivity to bleomycin (3.5-fold), etoposide (2.5-fold), camptothecin (3-fold) and mitomycin C (1.5-fold), but normal sensitivity towards UV-C. Despite the clear hypersensitivity towards DSB-inducing agents, the overall rates of DSB-rejoining in NBS cells as measured by pulsed field gel electrophoresis were found to be very similar to those of wild type cells. This indicates that the X-ray sensitivity of NBS cells is not directly caused by an overt defect in DSB repair.

Abnormalities, Multiple↗
PubMed1999

Targeted gene disruption reveals an adhesin indispensable for pathogenicity of Blastomyces dermatitidis.

Systemic fungal infections are becoming more common and difficult to treat, yet the pathogenesis of these infectious diseases remains poorly understood. In many cases, pathogenicity can be attributed to the ability of the fungi to adhere to target tissues, but the lack of tractable genetic systems has limited progress in understanding and interfering with the offending fungal products. In Blastomyces dermatitidis, the agent of blastomycosis, a respiratory and disseminated mycosis of people and animals worldwide, expression of the putative adhesin encoded by the WI-1 gene was investigated as a possible virulence factor. DNA-mediated gene transfer was used to disrupt the WI-1 locus by allelic replacement, resulting in impaired binding and entry of yeasts into macrophages, loss of adherence to lung tissue, and abolishment of virulence in mice; each of these properties was fully restored after reconstitution of WI-1 by means of gene transfer. These findings establish the pivotal role of WI-1 in adherence and virulence of B. dermatitidis yeasts. To our knowledge, they offer the first example of a genetically proven virulence determinant among systemic dimorphic fungi, and underscore the value of reverse genetics for studies of pathogenesis in these organisms.

Alleles↗
PubMed1999

The effect of canine macrophages on the adherence and growth of Blastomyces dermatitidis yeast: evidence of a soluble factor that enhances the growth of B. dermatitidis yeast.

Blastomycosis is a medically important systemic fungal infection of dogs and humans. Phagocytic cells are the first line of cellular defence against B. dermatitidis, and are a prominent feature in the lesions and exudate of canine blastomycosis. The adherence of B. dermatitidis yeast to canine phagocytes, and the effects of such adherence on the growth of B. dermatitidis yeast, has not been previously reported. The results of this study demonstrate that canine complement enhances the adherence of B. dermatitidis yeast to canine macrophages. Initiation of the canine complement cascade by B. dermatitidis yeast appeared to occur predominantly by the classical pathway. Adherence of B. dermatitidis yeast to canine macrophages enhanced the growth of the yeast. In the absence of macrophages, this effect could be duplicated by incubating yeast in conditioned medium from co-cultures of macrophages and yeast. This observation suggests that a soluble factor is involved in the growth enhancement of the yeast, These findings provide new insights into the adherence of B. dermatitidis yeast to canine macrophages, and how adherence influences the proliferation of B. dermatitidis yeast.

Animals↗
PubMed1999

Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease.

BACKGROUND: Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects. METHODS AND RESULTS: This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L; 1 allele, 15.7 +/- 5.1 nmol/L; 2 alleles, 17.3 +/- 4.7 nmol/L; P =.006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P =.001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents ( P <.05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5; 95% confidence intervals 1.1 to 2.1, P =.03, and 1.0 to 2.1, P =.05, respectively). CONCLUSIONS: The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.

Alleles↗
PubMed1999

The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens.

Plasmocyte selective monoclonal antibodies (MAb) recognizing syndecan-1 have recently been described. They belong to a new cluster, CD138. Using the MAb MI15, we investigated the expression of syndecan-1 in routinely paraffin-embedded tissues. Nontumoral lymph nodes (25 cases) and bone marrow biopsy specimens (63 cases) showed strong membrane staining of plasma cells only, allowing accurate analysis of the nuclear structure. The MI15 positivity correlated with kappa and lambda light chain expression in the cytoplasm. The percentages of plasma cells calculated in bone marrow biopsy specimens after MI15 staining were, respectively, 2.1% (range, 1% to 4%) in normal bone marrows, 8.5% (range, 5 to 17) in reactive plasmocytosis, and 4.66% in monoclonal gammapathy of undetermined significance (MGUS) patients (range, 1 to 13), in the same range but slightly higher than those obtained on smears or on hematoxylin and eosin (H&E)-stained sections. In multiple myeloma (40 cases), all plasma cell types were marked, and Mi15 MAb gave additional information in 8 of 40 (20%) patients. In lymph nodes, Mi15 MAb reacted with Reed-Sternberg cells of classical Hodgkin's disease in 23 of 31 cases (74%) with variable intensity. In contrast, nodular lymphocyte predominance Hodgkin's disease (10 cases), most B cell lymphomas (88 of 107 cases) and all T cell lymphomas (30 cases) were negative. In B cell lymphomas, plasmocytomas (8 cases), plasmocytic lymphomas (2 cases), and 5 of 13 cases of immunoblastic lymphoma with plasmocytoid differentiation were stained. In lymphoplasmocytoid lymphomas (4 lymph nodes and 20 bone marrow biopsy specimens), only mature plasma cells were positive. Moreover, a wide distribution of syndecan-1 was observed in normal and tumoral epithelial tissues. Finally, Mi15 MAb appears to be a reliable marker for identifying and quantifying normal and tumoral plasma cells in paraffin-embedded bone marrow and lymph node samples.

Antibodies, Monoclonal↗
PubMed1999

Lymph node revealing solution: a rapid method for the fixation of cystectomy specimens.

The objective of this study was to describe the use of the lymph node revealing solution (LNRS) for rapid fixation of total cystectomy specimens, and to compare it with formalin fixation. LNRS is a mixture of 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin (65:20:5:10 v/v) prepared under a fume-hood. Sixteen consecutive cystectomy specimens were fixed for two hours either in LNRS or in buffered formalin. Representative sections were embedded in paraffin, sectioned and stained with H&E, periodic acid Schiff, alcian-blue, and immunostained for cytokeratins 20, high and low molecular weight cytokeratins, prostatic specific antigen, Factor VIII related antigen, s-100 protein, and protein kinase C isoenzymes. Results showed that the tissues were well fixed after 2 hours in LNRS, and were not fixed after 2 hours in formalin. Processing and sectioning of the paraffin blocks of the LNRS fixed tissue was excellent; it was impossible in the sections fixed for 2 hours in formalin. All the stains were excellent after LNRS fixation. We conclude that fixation of cystectomy specimens in LNRS requires only two hours and results in excellent stained slides. It is therefore recommended for cystectomy specimens.

Biomarkers, Tumor↗
PubMed1999

Dendritic cell-based vaccine: a promising approach for cancer immunotherapy.

The unique ability of dendritic cells to pick up antigens and to activate naive and memory CD4+ and CD8+ T cells raised the possibility of using them to trigger a specific anti-tumor immunity. If numerous studies have shown a major interest in dendritic cell-based vaccines for cancer immunotherapy in animal models, only a few have been carried out in human cancers. In this review, we describe recent findings in the biology of dendritic cells that are important to generate anti-tumor cytotoxic T cells in vitro and we also detail clinical studies reporting the obtention of specific immunity to human cancers in vivo using reinfusion of dendritic cells pulsed with tumor antigens.

Antigens, Neoplasm↗
PubMed1999

Antenatal visualization of vascular anastomoses in monochorionic twins using color Doppler sonography: the protective function of these anastomoses and the phenomenon of interference beating.

This report concerns the antenatal visualization and velocimetry of an arterioarterial and a venovenous anastomosis in a monochorionic twin pregnancy using color Doppler sonography. The phenomenon of 'interference beating' occurs when two flow velocity waveforms are superimposed in one blood vessel. This characteristic image can be generated antenatally to confirm the existence of a vascular communication. We were able to reveal these anastomoses postnatally using the dye injection technique.

Adult↗
PubMed1999

An agonist anti-human CD40 monoclonal antibody that induces dendritic cell formation and maturation and inhibits proliferation of a myeloma cell line.

CD40, a 48-50 KD cell membrane molecule, member of the nerve growth factor receptor and tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Anti-CD40 monoclonal antibody (MAb) has been shown earlier to costimulate with IgM or phorbol esters resting B cells to proliferate, differentiate, secrete immunoglobulins, and switch isotype. Here we report on an agonistic mouse anti-human CD40 MAb 5C11. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-CD40 MAb 89. We studied the effects of MAb 5C11 on a multimyeloma cell line, XG2, that expresses the CD40 antigen strongly and found that this MAb caused the homotypic aggregation of XG2, strongly suppressed XG2 proliferation, and led to its apoptosis after 24 hr of treatment. Interestingly, MAb 5C11 also triggered the generation, proliferation, and maturation of dendritic cells from peripheral blood monocytes, either by itself or in combination with GM-CSF and IL-4.

Animals↗
PubMed1999

The contact of human macrophages with extracellular matrix proteins selectively induces expression of proinflammatory cytokines.

The interaction of macrophages with proteins of the extracellular matrix (ECM) is important for the regulation of the immune and nonimmune functions displayed by these cells. Little, however, is known about the ability of different ECM proteins to transmit inflammatory signals into macrophages. Here we investigated the effect of the ECM proteins collagen type I, fibrin and fibronectin on the expression of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-8 using RT-PCR, Northern and Western blot analysis and ELISA technique. It was found that collagen strongly induced IL-1beta and IL-8 expression in the macrophages. Fibronectin also stimulated cytokine expression, however, the amounts of the specific mRNAs were significantly lower compared to those induced by collagen. On the protein level IL-1beta revealed a close correlation to the mRNA expression. In contrast, fibrin did not elicit any IL-1beta and IL-8 response. These data show that different ECM proteins vary in their ability to induce proinflammatory cytokine expression in human macrophages suggesting that the protein composition of the ECM might be crucial in the initiation of inflammatory processes.

Blotting, Northern↗
PubMed1999

Interleukin-10 and Gp130 cytokines in human multiple myeloma.

Interleukin (IL)-10 is a critical cytokine involved in the terminal differentiation of B cells into plasma cells. IL-10 is also involved in multiple myeloma, a malignant plasma cell disorder. IL-6 and, more generally the cytokines activating the gp130 IL-6 transducer, are major survival and proliferation factors of myeloma cells. IL-10 is also a growth factor of malignant plasma cells, produced by myeloma cells from about half the patients and is detected in the plasma of patients with plasma cell leukemia or solitary plasmacytoma. The myeloma cell growth activity of IL-10 is mediated through a gp130 cytokine, oncostatin M (OSM), that is frequently produced by myeloma cells. Myeloma cells fail to express OSM receptors but IL-10, by inducing it, confers on them the sensitivity to OSM.

Animals↗