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Biomedical subjects

B Klein

Publications and source records attributed to B Klein.

At least 109 records · Page 6Linked to original sources
PubMed1997

Lymph node-revealing solution: simple new method for detecting minute lymph nodes in colon carcinoma.

PURPOSE: Detection of metastatic lymph nodes in colon cancer is essential for determining stage and, thus, therapeutic modalities. However, very small lymph nodes can easily be missed during routine examination. The aim of this study is to describe a new and easy technique for detecting tiny nodes in colonic specimens. METHODS: Thirty problematic cases, in which an unsatisfactory number of lymph nodes was found by the traditional method, were investigated. The entire mesocolonic fat was immersed for six hours in a lymph node-revealing solution (LNRS) composed of various traditional fixatives and fatty solvents. After six hours, the lymph nodes stood out as white, chalky nodules on the background of yellow fat. They were then excised, processed. and stained. RESULTS: Total number of lymph nodes found by the traditional method in the 30 cases was 88. After LNRS, 258 additional lymph nodes, measuring from 0.5 to 7 mm in largest diameter, were found. Of the 12 cases in which no lymph nodes were found by the traditional method, 8 became N0 and 4 became N1. Of the 14 cases first classified as N0, 4 became N1; of the 4 classified at first as N1, 2 became N2 after LNRS. Upstaging from Dukes B to C occurred in eight cases. Quality of the sections and histochemical and immunohistochemical stains after LNRS was similar to that of formalin-fixed tissues. CONCLUSIONS: LNRS is an easy, rapid, and inexpensive technique for detecting very small lymph nodes. These may contain metastases, a fact that changes the stage of disease and influences the mode of therapy.

Acetic Acid↗
PubMed1997

Monocyte-biomaterial interaction inducing phenotypic dynamics of monocytes: a possible role of monocyte subsets in biocompatibility.

For the in vitro study of cell-biomaterial surface interactions, the choice of cell type is crucial. In vivo data indicate that during the healing of the implant in the tissues, the pivotal cell types are the macrophages. These cells, upon interaction with any foreign material, might initiate a spectrum of responses, which could lead to acute and chronic inflammatory changes affecting the biocompatibility of the implant. Whether the mechanisms governing the type of evolving inflammatory reaction could be attributed to the macrophages functional differentiation mirrored by monocyte subsets during the polymer interaction, is poorly described. This in vitro study, therefore, attempted to investigate whether different biomaterials influence monocyte cellular activity, determined by the myeloperoxidase level and mitochondrial XTT cleavage, and phenotype dynamics characterized by the presence of CD14, RM 3/1 and 27E10 antigens. It is shown that different polymers exert differential potential to influence monocytes, both in their cellular activity and their phenotypic pattern. Thus, these findings demonstrating material-induced monocyte activation and monocyte phenotype modulation, are suggestive of the monocyte role as reporter cells in evaluating the biocompatibility of a synthetic medical device.

Journal Article↗
PubMed1997

Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma.

The pathogenesis of multiple myeloma (MM), an incurable tumour causing the deregulated proliferation of terminally differentiated B cells, is unknown. Chromosomal translocations (14q1) affecting band 14q32 and unidentified partner chromosomes are common in this tumour, suggesting that they may cause the activation of novel oncogenes. By cloning the chromosomal breakpoints in an MM cell line, we show that the 14q+ translocation represents a t(6;14)x(p25;q32) and that this aberration is recurrent in MM, as it was found in two of eleven MM cell lines. The translocation juxtaposes the immunoglobulin heavy-chain (IgH) locus to MUM1 (multiple myeloma oncogene 1)/IRF4 gene, a member of the interferon regulatory factor (IRF) family known to be active in the control of B-cell proliferation and differentiation. As a result, the MUM1/IRF4 gene is overexpressed--an event that may contribute to tumorigenesis, a MUM1/IRF4 has oncogenic activity in vitro. These findings identify a novel genetic alteration associated with MM, with implications for the pathogenesis and diagnostics of this tumour.

Animals↗
PubMed1997

Lymph-node revealing solution: a new method for detecting minute lymph nodes in cystectomy specimens.

OBJECTIVE: To describe the use of a new lymph-node revealing solution (LNRS) for detecting lymph node involvement in total cystectomy specimens from patients with locally confined invasive transitional cell carcinoma (TCC) of the bladder, and to compare the results obtained with those using the conventional method (palpation and sectioning perivesical fat) that may fail to detect very small lymph nodes. MATERIALS AND METHODS: Of 12 cystectomy specimens obtained from patients with TCC, six in which 0-3 metastatic nodes were identified by the conventional method were further investigated using LNRS. The revealing solution comprised 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin (65:20:5:10 v/v) prepared under a fume-hood. After evaluation using the conventional method, the specimens were immersed for 6-12 h in the solution, washed under running tap water and the adipose tissue sectioned at intervals of 2-3 mm. Lymph nodes were identified as white, chalky nodules against the background of yellow fat. The number of the lymph nodes identified by conventional and the LNRS methods was recorded and classified according the TNM system. RESULT: Twenty-two lymph nodes were detected by the conventional method, of which four were positive for tumour metastasis. Using the LNRS, an additional 21 nodes were identified among which 12 were positive. The mean size of the lymph nodes detected by the conventional and LNRS methods was 7.96 mm and 3.81 mm, respectively. The stage of three patients was increased (Nx to N2, N0 to N2 and N1 to N2) and therefore two of these patients received adjuvant chemotherapy. CONCLUSIONS: LNRS significantly enhanced the yield of normal and metastatic nodes of cystectomy specimens and may identify smaller nodes. The LNRS method allows a more accurate staging with better assessment of the prognosis and need for adjuvant therapy.

Carcinoma, Transitional Cell↗
PubMed1997

Rhinovirus-specific T cells recognize both shared and serotype-restricted viral epitopes.

To characterize rhinovirus (RV)-specific T cells, RV16- and RV49-specific CD4 T cells were cloned from peripheral blood, and cytokine secretion and serotype specificity were defined. Each RV-specific clone secreted high levels of interferon-gamma, and several also produced interleukin-4 and -5. To test serotype specificity, each clone was incubated separately with five different RV serotypes. Although 2 of 31 clones proliferated only in response to the virus used in cloning, the rest had significant proliferation in response to 2-5 different serotypes. Thus, RV-specific T cells can be activated by either serotype-specific or shared viral epitopes, raising the possibility that repeated activation of T cells by shared viral determinants in vivo could induce potent recall T cell responses. It is likely that enhanced T cell responses to shared viral epitopes contribute to antiviral activity, airway inflammation, or both.

Antigen-Presenting Cells↗
PubMed1997

Both human alpha/beta and gamma interferons upregulate the expression of CD48 cell surface molecules.

We have established a cDNA library from interferon (IFN)-treated human lymphoblastoid Daudi cells and made use of differential screening to search for yet unidentified IFN-regulated genes. In the course of these studies, we have isolated a human cDNA coding for the glycosyl-phosphatidylinositol-linked (GPI) membrane glycoprotein CD48 (TCT-1, Blast-1). Various studies demonstrated that the murine CD48 is the predominant counterreceptor for the mouse CD2 and is involved in the regulation of T cell activation. Since the murine CD48 is functionally homologous to the human CD2 ligand LFA-3 (CD48), the function of the human CD48 remains unknown. In this report, we show that both Hu-IFN-alpha/beta and Hu-IFN-gamma increase the level of CD48 mRNA and upregulate the expression of CD48 proteins at the surface of various cultured human cell lines. However, the IFN have no effect on the expression of LFA-3. In addition, we show that IFN increase CD48 expression on peripheral blood mononuclear CD3+, CD14+, and CD19+ subpopulations. These data suggest that in addition to modulation of the conventional MHC class I and class II-restricted interactions, the IFN might promote MHC-unrestricted interactions of target cells with the immune cells by inducing the expression of the cell surface CD48 molecule.

Antigens, CD↗
PubMed1997

Successful induction and consolidation therapy of acute myeloid leukaemia in a renal allograft recipient.

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible.

Adult↗
PubMed1997

Lymph node revealing solution: a new method for detection of minute axillary lymph nodes in breast cancer specimens.

The staging and prognosis of patients with breast cancer is related to the presence or absence of axillary lymph node involvement. However, in some cases no lymph nodes or too small a number of lymph nodes are revealed by the traditional method of palpating and sectioning the axillary fat. In the present study we demonstrate the usefulness of the lymph node revealing solution (LNRS) in breast cancer. Specimens from 13 patients, in whom <10 lymph nodes were identified in the axilla by the traditional method, were included in the study. After excising the lymph nodes by the traditional method, axillary tissue was immersed in LNRS for 6-12 hours. Additional lymph nodes, which stood out as white chalky nodules, were excised and processed as usual. The LNRS increased the mean number of nodes per case from 6.0+/-2.5 found by the traditional method to 12.54+/-4.61 nodes per case (p < 0.01). The size of the nodes identified by the LNRS was significantly smaller (p < 0.01) than those detected by the traditional method. The LNRS changed the lymph node stage of the disease in four of the studied cases (30%). LNRS seems to be the technique of choice for detection of axillary lymph nodes in cases where the number of detected lymph nodes by the traditional method is too small for accurate staging.

Axilla↗
PubMed1997

Activation, binding, and processing of complement component 3 (C3) by Blastomyces dermatitidis.

Complement plays a key role in phagocyte recognition and killing of Blastomyces dermatitidis, but little is known about how complement components interact with the yeast. We report the characteristics of activation, binding, and processing of C3 by B. dermatitidis. In pooled normal human serum (NHS), deposition of C3 on the yeast was detectable within 2 min, whereas in NHS containing MgEGTA, deposition was delayed by 6 min, indicating that the yeast activates C3 by both classical and alternative pathways. When both pathways were operative, maximal binding of 4.5 x 10(6) C3 molecules/cell was achieved in less than 30 min. In the absence of the classical pathway, yeast cells bound 80% of the maximum C3, indicating that the yeast intrinsically activates the alternative pathway. Delayed deposition of C3 in NHS-MgEGTA was similar to that in NHS preabsorbed by the yeast or by immobilized protein A/G to remove serum immunoglobulin. Purified immunoglobulin restored C3 binding to NHS preabsorbed by the yeast, suggesting that antibody in nonimmune serum initiates the classical pathway. beta-Glucan absorption of NHS abolished the classical pathway, suggesting that cell wall beta-glucan is a target of initiating antibodies. Hydroxylamine treatment of NHS-opsonized yeast cells showed that 76% of C3 was bound to yeast cells by ester linkage, supporting a role for hydroxyl groups on cell wall polysaccharides. Hydroxylamine-cleaved fragments were chiefly C3b and iC3b; 70% of hydroxylamine-sensitive C3b was converted to iC3b within 1 min of opsonization, and the ratio was stable over 1 h. Our data predict that C3b and iC3b on opsonized yeast cells direct binding to CR1 and CR3 receptors on human phagocytes, which, in turn, may influence the fate of this host-pathogen interaction.

Blastomyces↗
PubMed1997

Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity.

The IL-6 receptor system comprises two functionally different chains: a binding chain (IL-6R) and a signal-transducing chain (gp130). The IL-6/IL-6R complexes associate with gp130, induce its dimerization and signal transduction. When IL-6 is complexed to IL-6R, two distinct sites of IL-6 are able to bind gp130. Other cytokines-oncostatin M (OM), leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) also use the gp130 transducer and induce its heterodimerization with LIF receptor (LIFR). A series of IL-6 mutants have been generated which function as IL-6 receptor antagonists (IL-6RA). These IL-6RA carried substitutions that increased their affinity with IL-6R and abolished 1 or the 2 sites of interaction with gp130. All the IL-6RA inhibited wild-type IL-6. The IL-6RA with one mutated binding site to gp130 inhibited IL-11 activity. They did not affect those of CNTF, LIF and OM, even when used at a very high concentration at which virtually all membrane IL-6R were bound to IL-6RA. IL-6RA with two mutated gp130 binding sites did not affect IL-11, CNTF, LIF or OM activities. The results indicate that the interaction of one gp130 chain with IL-6R/IL-6R complexes inhibited further the dimerization of gp130 induced by IL-11/IL-11R but not its heterodimerization with LIFR. Thus these IL-6RA can also function as IL-11 antagonists.

Antigens, CD↗
PubMed1996

Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop.

We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL-10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia-inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL-10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG-6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.

Antigens, CD↗
PubMed1996

Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease.

BACKGROUND: Previous research has shown that the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is a major determinant of plasma ACE activity. It has been suggested that persons with the DD genotype (those who express, on average, the highest levels of circulating ACE) have an increased risk for myocardial infarction and coronary artery disease, particularly if they are otherwise at low risk. Subsequent studies, however, have not confirmed that ACE I/D gene polymorphism is a risk factor for coronary artery disease and myocardial infarction. OBJECTIVE: To investigate the association between the I/D polymorphism of the ACE gene and the risk for coronary artery disease and myocardial infarction in patients in whom coronary artery disease status was documented by angiography. DESIGN: Cross-sectional study. SETTING: University medical center. PATIENTS: 209 male case-patients with coronary artery disease and 92 male controls without coronary artery disease, as documented by coronary angiography. MEASUREMENTS: Assessment of the cardiac risk profile by questionnaire; classification of patients by the degree of coronary artery stenosis; levels of lipoproteins, apolipoproteins, and fibrinogen; and ACE I/D gene polymorphism assessed by polymerase chain reaction amplification. RESULTS: Plasma ACE activity was significantly associated with ACE I/D gene polymorphism. The ACE genotype was not associated with the presence of coronary artery disease or myocardial infarction. If a recessive effect of the D allele was assumed (DD compared with DI and II), the relative risk was 1.00 (95% CI, 0.76 to 1.30) for coronary artery disease and 1.03 (CI, 0.77 to 1.38) for myocardial infarction. Results of analyses were also negative when a dominant effect of the D allele was assumed and when low-risk subgroups were examined. The established risk factors age and apolipoprotein B level emerged as the most important risk predictors in multivariate analyses, followed by diastolic blood pressure and fasting glucose levels. CONCLUSIONS: In an angiographically defined study sample, ACE I/D gene polymorphism was not associated with an increased risk for coronary artery disease or myocardial infarction, despite its effects on plasma ACE activity.

Aged↗
PubMed1996

[Head and neck sarcoma].

We reviewed patients with primary soft tissue and bone sarcomas treated in our department. Malignant tumors arising in somatic, connective, soft tissues, especially those of the head and neck, are uncommon and few reports have been published. Between 1980 and 1995 15 patients with head and neck sarcoma were seen. The major sites involved included: paranasal sinuses and orbits (2 patients), neck (4) and 1 each in the forehead, temporal region, mandible, parapharyngeal space, tongue, hypopharynx, larynx, cervico-mediastinal region and nasal cavity. Follow-up ranged from 1-16 years. The youngest patient was a 12-year-old male. Rhabdomyosarcoma, one of the most common mesenchymal tumors found in the head and neck, especially in children, was excluded from our study because of its different clinical behavior and its chemosensitivity, unlike other sarcomas. Most of our patients were treated with wide-field resection; 12 received postoperative radiation, and 3 combined surgery and chemotherapy. Wide excision with negative margins is considered an important, positive, prognostic factor, as the extent and adequacy of excision largely determines survival and the incidence of local recurrence. All our patients underwent initial, wide, local excision of the lesion. Our observations strongly suggest that wide resection is the most effective means of therapy for sarcoma of the head and neck. Radical neck dissection was not only performed for manifest regional neck metastases, but was also used for completing the enlarged, wide-excisions of liposarcomas. The worst survival was in patients with osteosarcoma, angiosarcoma and fibrosarcoma, with an absolute 5-year survival of 60% (9/15).

Adult↗
PubMed1996

Human interleukin-6 receptor super-antagonists with high potency and wide spectrum on multiple myeloma cells.

Interleukin-6 (IL-6) is the major growth factor for myeloma cells and is believed to participate in the pathogenesis of chronic autoimmune diseases and postmenopausal osteoporosis. IL-6 has been recently shown to possess three topologically distinct receptor binding sites: site 1 for binding to the subunit specific chain IL-6R alpha and sites 2 and 3 for the interaction with two subunits of the signaling chain gp130. We have generated a set of IL-6 variants that behave as potent cytokine receptor super-antagonists carrying substitutions that abolish interaction with gp130 at either site 2 alone (site 2 antagonist) or at both sites 2 and 3 (site 2 + 3 antagonist). In addition, substitutions have been introduced in site 1 that lead to variable increases in binding for IL-6R alpha up to 70-fold. IL-6 super-antagonists inhibit wild-type cytokine activity with efficacy proportional to the increase in receptor binding on a variety of human call lines of different origin, and the most potent molecules display full antagonism at low molar excess to wild-type IL-6. When tested on a representative set of IL-6-dependent human myeloma cell lines, although site 2 super-antagonists were in general quite effective, only the site 2 + 3 antagonist Sant7 showed antagonism on the full spectrum of cells tested. In conclusion, IL-6 super-antagonists are a useful tool for the study of myeloma in vitro and might constitute, in particular Sant7, effective IL-6 blocking agents in vivo.

Antigens, CD↗
PubMed1996

Vertical Flux of Biogenic Carbon in the Ocean: Is There Food Web Control?

Models of biogenic carbon (BC) flux assume that short herbivorous food chains lead to high export, whereas complex microbial or omnivorous food webs lead to recycling and low export, and that export of BC from the euphotic zone equals new production (NP). In the Gulf of St. Lawrence, particulate organic carbon fluxes were similar during the spring phytoplankton bloom, when herbivory dominated, and during nonbloom conditions, when microbial and omnivorous food webs dominated. In contrast, NP was 1.2 to 161 times greater during the bloom than after it. Thus, neither food web structure nor NP can predict the magnitude or patterns of BC export, particularly on time scales over which the ocean is in nonequilibrium conditions.

Journal Article↗
PubMed1996

Anti-gp130 transducer monoclonal antibodies specifically inhibiting ciliary neurotrophic factor, interleukin-6, interleukin-11, leukemia inhibitory factor or oncostatin M.

Five cytokines activate the gp130 IL-6 transducer: ciliary neurotrophic factor, interleukin-6, interleukin-11, leukemia inhibitory factor and oncostatin M. Human plasmacytoma cell lines, completely dependent on the addition of one of these five cytokines for their growth, were used to obtain anti-gp130 monoclonal antibodies specifically inhibiting one of these five cytokines without affecting the biological activity of the others. These antibodies should improve our understanding of the interaction of gp130 transducer using cytokines with gp130 transducer and facilitate the design of new cytokine inhibitors.

Antibodies, Monoclonal↗