Biomedical subjects

R Benner

Publications and source records attributed to R Benner.

At least 55 records · Page 3Linked to original sources

PubMed1993

Autoimmunity, hyporeactivity to T cell mitogens and lymphoproliferative disorders following neonatal induction of transplantation tolerance in mice.

We have reported that, in A/J (A) (H-2a) mice, a partial tolerance to C57BL/10ScSn (B10) (H-2b) skin allografts and a high incidence of lethal lymphoproliferative disorders (LPD) can be induced by the neonatal i.v. injection of 2 x 10(7) semiallogeneic (B10 x A)F1 spleen cells (SC) (Végh, P., Baranyi, L. and Jánossy, T., Cell. Immunol. 1990, 129: 56). In this study, we show that the incidence and mortality of LPD were continuously growing from 1 month of age until the end of the experiment at 1 year (64% and 36%, respectively). Based on histology, 27% of the diseased mice suffered from lymphoid malignancies. In the remaining cases (73%), reactive histopathological changes were seen in the spleen, lymph nodes (LN), liver and kidneys. The proportion of CD4+ T cells in the spleen and LN as well as that of splenic B cells decreased, while the percentages of mature and immature myeloid cells doubled. The total cell number of each (sub)population, however, was elevated in both lymphoid organs. The cells taking part in the lymphoproliferation were of host (A) and not of donor (F1) origin. Preceding the development of apparent LPD, the SC, LN cell and thymus cell suspensions of 1-month-old tolerized mice showed reduced in vitro proliferative responses to T cell and T cell-dependent B cell mitogens (Con A or PWM), while their reactivity to a T cell-independent B cell mitogen (lipopolysaccharide) was essentially unimpaired. This hyporeactivity seems to be functional, because neither histology nor immunophenotyping by flow cytometry revealed significant alterations in the spleen and thymus of such animals, apart from a slight reduction in the ratio of CD4+/CD8+ T cell subpopulations in the spleen. The in vivo T cell-mediated immune response of the tolerized mice was practically normal to third party CBA/Ca (H-2k) allografts. Antithymocyte autoantibodies (ATA) were detected in the sera of 76% of the tolerized mice at 1 month of age (i.e., even before the mass appearance of LPD). ATA as well as antinuclear Ab were present in 65% of the adult tolerized mice, independently of the presence of LPD. Taken together, in A mice neonatally injected with (B10 x A)F1 SC, a partial, specific allograft tolerance and a chronic host-vs.-graft disease-like syndrome developed. The latter is manifested in hyporeactivity to T cell mitogens, development of autoantibodies and, subsequently, in progressive LPD and lymphoid malignancies.

Animals↗

PubMed1993

MHC-specific graft-protective and delayed-type hypersensitivity (DTH) suppressive activity of a CD4+ CD8+, alpha beta T cell receptor (TCR) positive lymphoma isolated from a tolerant mouse.

Two lymphomas were found in, and isolated from A (H-2a) mice in which permanent transplantation tolerance was induced to CBA (H-2k) histocompatibility antigens by the neonatal injection of (CBAxA)F1 spleen cells. They proved to be of recipient origin and were transferable to syngeneic A mice, growing as disseminated lymphomas (L33 and L46) and killing the recipients rapidly. Analysis of the cell surface antigens disclosed that both lymphomas had an immature T cell phenotype [Thy-1+, CD5+, CD3low, TCR alpha beta low, CD4low, CD8high, heat-stable antigen (HSA) positive, and CD44-, MHC class II-, CD45R-, sIg-, Gr-1-, CD11b-]. Intraperitoneal (i.p.) injection of syngeneic A mice with viable L33 lymphoma cells resulted in a dose-dependent, significant prolongation of the mean survival times of "specific" CBA and MHC-identical B10.BR skin allografts as compared to the survival of appropriate grafts in non-lymphoma-bearing controls. The survival times of third party MHC-incompatible B10 (H-2b) and B10.D2 (H-2d) allografts were only slightly prolonged in A mice inoculated with L33 cells. The graft-protective effect was not abrogated if the proliferative capacity of the L33 cells was blocked by in vitro mitomycin C (MMC) pretreatment. Furthermore, the inoculation of L33 lymphoma into A mice significantly inhibited their DTH response to the sensitizing CBA histocompatibility antigens. In contrast, the L46 lymphoma had no effect on the survival of CBA allografts and the DTH reactivity. These data suggest that the CD4+CD8+TCR alpha beta + L33 T cell lymphoma originating from a neonatally tolerant mouse has a specific immunosuppressive effect on the in vivo reactivity of syngeneic mice to the tolerance-inducing (MHC class I) alloantigens.

Animals↗

PubMed1992

Improved survival from potentially lethal graft-vs.-host disease by donor pretreatment with a recipient-specific blood transfusion. I. Requirements for induction and specificity of the effect.

Pretreatment of prospective donors of hemopoietic cells with a single recipient-specific blood transfusion can significantly decrease the morbidity and mortality of graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice. This beneficial effect of donor pretreatment could be demonstrated in donor-recipient strain combinations that were H-2 + non-H-2, H-2, or only class II-disparate, but not in the class I-disparate C57BL-B6.C-H-2bm1 strain combination. The effect was proportional to the amount of recipient-strain blood used for transfusion. Donor transfusion with a single dose of 1 ml recipient-specific whole blood resulted in minimum GVHD, lower doses being less or not effective. The interval between donor pretreatment and the use of their hemopoietic cells for reconstitution appeared to be important. The best survival was found at an interval of 4 days. Multiple transfusion was not more effective than a single one. We compared the effectiveness of whole blood and irradiated spleen cells for donor pretreatment. Both protocols have been shown previously to suppress anti-recipient delayed-type hypersensitivity. It appeared that the blood transfusion protocol was superior to the spleen cell protocol. The beneficial effect appeared to be recipient specific, since a third-party blood transfusion did not improve GVHD. We found that the beneficial effect of donor blood transfusion was due to suppression of the anti-host immune response. The donor blood transfusion was able to induce bystander suppression to alloantigens that were not used for the induction of suppression, provided they were co-expressed with the specific alloantigens by the recipients. This also indicates that, although the induction of suppression is specific, the ultimate suppressive effect is non-specific.

Animals↗

PubMed1992

Prevention of lethal graft-versus-host disease by monoclonal antibody treatment in vivo.

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). The disease is caused by mature T cells in the graft that recognize foreign antigens of the host and subsequently elicit an immune response to host tissues. Although T-cell depletion of the graft strongly reduced the incidence and severity of GVHD, the overall survival of allogeneic BMT did not increase because of the increased rate of graft rejection and leukemic relapses. New prophylactic and therapeutic approaches have to be developed to improve the outcome of allogeneic BMT. T-cell-specific monoclonal antibodies (mAb) administered in vivo to the allograft recipients seem to be promising in the prevention and treatment of lethal GVHD. In this study we especially addressed the effect of in vivo treatment of recipients with anti-T-cell subset mAb in a murine model for acute GVHD. We also determined the long-term effects.

Animals↗

PubMed1992

Cytokines in lethal graft-versus-host disease.

Graft-versus-host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens on host tissues. This leads to T cell activation, which involves a cascade of events including the transcription of genes for cytokines and their receptors and the production of cytokines. One of the first cytokines to appear is interleukin 2 (IL-2). IL-2 production enhances the IL-2 receptor expression and leads to T cell proliferation. As a further step, differentation of T cells occurs, which results in the production of a certain pattern of cytokines. These cytokines influence the expression of cell surface antigens and adhesion molecules, and are able to activate other cell types such as cytotoxic T cells, macrophages and natural killer cells, which might act as effector cells in tissue destruction. Insight into the sequential expression of the various cytokines involved might enable a more effective treatment of GVHD. Therefore, we investigated the occurrence of cytokines in a murine model for acute GVHD. We addressed in particular the period early after allogeneic reconstitution.

Animals↗

PubMed1991

Prevention of lethal graft-vs.-host disease by a single low dose injection of anti-T cell monoclonal antibody to the allograft recipients.

We investigated the capacity of monoclonal antibody (mAb) treatment to prevent graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice, employing anti-T cell (subset) mAb and a fully allogeneic strain combination. In this strain combination, purified CD4+ cells were able to induce a lethal GVH reaction, whereas purified CD8+ cells were not. In the same strain combination, a single intraperitoneal injection of IgG2b anti-Thy-1 mAb, one day after reconstitution, caused a dose-dependent improvement of the survival. A single injection of a dose as low as 12.5 micrograms per mouse was already effective. Intravenous and intraperitoneal administration of the mAb appeared equally effective. For effective prevention of GVHD the treatment could be postponed until the 4th day after transplantation, but treatment delayed until day 6 was no longer effective. Treatment with IgG2b mAb specific for either helper or cytotoxic T cells also led to improvement of GVHD and survival, but was less effective than treatment with anti-Thy-1 mAb. Clinically, there was a difference in the effectiveness of anti-CD4 and anti-CD8 treatment, since symptoms of GVHD started earlier in the anti-CD8 treated group and the survival was better in the anti-CD4 treated group. These results press for prospective clinical studies employing anti-T cell mAb treatment early after allogeneic bone marrow transplantation, especially in HLA mismatched cases.

Animals↗

PubMed1991

Isolation and molecular characterization of the B cells producing the paraprotein in a case of benign monoclonal gammapathy in C57BL mice.

Benign monoclonal gammapathy (BMG) is defined as a benign monoclonal B cell proliferative disorder characterized by the presence of a persisting component of homogenous immunoglobulins (H-Ig) in the serum. A possible role of antigenic stimulation in the development of BMG has been suggested. From a C57BL mouse, a murine model for BMG, we have isolated clonally related B cells in order to investigate the occurrence of somatic mutations in the variable heavy chain (VH) region of the genes of H-Ig-producing B cell clones. Therefore, B cells were immortalized by hybridoma technology. The hybridomas were screened for resemblance of the serum H-Ig component by Wieme agar electrophoresis, followed by immunoblotting and isoelectrofocusing. Clonal relationship was investigated by Southern blot analysis using a JH probe. In this way we isolated five hybridomas producing an IgG2a, kappa that was identical to the original serum H-Ig component according to testing with anti-idiotypic antisera. mRNA sequencing of four hybridomas showed only one base pair difference in the VH genes. This particular gene belonged to the J558 VH gene family. When compared to the most closely related known VH sequence, three base pair differences were found. The almost complete absence of base pair differences in the VH genes of the four sequenced hybridomas, compared with an independently derived hybridoma, suggests that the same germ-line VH gene has been used and that somatic mutations were infrequent in our BMG clone.

Animals↗

PubMed1991

Hyperthyroid myopathy and the response to treatment.

Hyperthyroidism is accompanied by significant dysfunction of both proximal and distal skeletal muscles. The purpose of this study was to quantitate the degree of muscle weakness in newly diagnosed patients with Graves' disease and to assess the response to treatment. Ten patients were prospectively studied with objective measures of strength and endurance of proximal and distal muscles while hyperthyroid (stage I), after 2 weeks of propranolol (stage II), and about 6 months later when euthyroid (stage III). Propranolol treatment for 2 weeks resulted in a subjective decrease in weakness, which was accompanied by a statistically significant improvement in grip strength (P less than 0.01), shoulder strength (P less than 0.02), and grip endurance (P less than 0.01) but not shoulder endurance. Muscle function further improved and attained control levels when the patients were chemically and clinically euthyroid. In contrast, a control group subjected to the same muscle testing protocol before and after 1 week of propranolol treatment showed no improvement in grip, shoulder strength, or shoulder endurance but had decreased grip endurance (P less than 0.01) and increased subjective weakness. These results confirm that muscle weakness commonly is associated with hyperthyroidism and can be quantitatively profound. In contrast to the effects of beta-blockade in normal controls, propranolol partially improves muscle weakness in thyrotoxic patients. We conclude that thyroid hormone and catecholamines in concert mediate the muscle dysfunction of hyperthyroidism.

Adrenergic beta-Antagonists↗

PubMed1991

Suppression of graft-versus-host reactivity by a single host-specific blood transfusion to prospective donors of hemopoietic cells.

Delayed-type hypersensitivity responses against recipient's histocompatibility antigens can occur early in the course of a graft-versus-host reaction in lethally irradiated allogeneically reconstituted mice. This reactivity could be suppressed by a single host-specific blood transfusion to the prospective donors of allogeneic spleen cells. Maximum suppression was found when the blood transfusion was given 4 or 5 days before the mice were used to reconstitute lethally irradiated hosts. Whole blood and purified white blood cells were capable of inducing suppression, whereas purified red blood cells, plasma, and serum were not. Suppression was already detectable after administration of 1 microliters of whole blood and virtually complete at a dose of 1.0 ml. Irradiation of the blood reduced but did not abrogate its capacity to induce suppression. Purified B and purified T lymphocytes appeared equally effective in inducing suppression. Two helper T cells clones, a Th1 and a Th2 clone, were able to induce suppression as well. A high dose of recombinant IL-2, injected daily for 5 days after reconstitution, did not abrogate or reduce the suppression. Suppression could be induced by H-2 as well as non-H-2 alloantigens, separately or together. A pure H-2-incompatible transfusion was more effective in inducing suppression than a pure non-H-2-incompatible one. Suppression appeared to be a dominant phenomenon and was mediated by a Thy-1+, CD4+, CD8- spleen cell population. This T cell population had its origin in the transfused donor, which excludes the possible involvement of blood-derived "veto-cells."

Animals↗

PubMed1991

The autologous mixed epidermal cell-T lymphocyte reaction is elevated in psoriasis: a crucial role for epidermal HLA-DR+/CD1a- antigen-presenting cells.

The objective of this study was to determine whether epidermal cells (EC) from psoriasis lesions and uninvolved skin could stimulate autologous T lymphocytes in the in vitro autologous mixed epidermal cell-T lymphocyte reaction (autologous MECLR). The functional role of antigen-presenting cell (APC) subsets was concurrently determined in this reaction. Mononuclear cells and purified T lymphocytes from peripheral blood of psoriasis patients showed a clear proliferative response to autologous unpurified epidermal cells from involved as well as uninvolved skin. The autologous mixed leukocyte reaction (MLR) was not elevated in psoriasis patients. In healthy controls and contact allergy patients, T-lymphocyte proliferation was not observed either in the autologous MECLR or in the autologous MLR. The level of proliferation in the autologous MECLR from psoriasis patients correlated to the number of epidermal cells that were added. To exclude the possibility that the observed proliferation in the autologous MECLR in psoriasis was due to the presence of epidermal T lymphocytes that were being stimulated and expanded in vitro, the stimulator EC were gamma irradiated (30 Gy) in some experiments. Preincubation of EC with cyclosporin A (CsA) significantly inhibited the autologous MECLR. The CsA-induced inhibition could be neutralized by the addition of fresh untreated EC to these cultures. This indicated that one of the modes of action of CsA in resolving psoriasis is, as some investigators have already shown, via inhibition of epidermal accessory cell function. In the autologous MECLR, APC from psoriasis skin could initiate this reaction, whereas APC from peripheral blood could not. This occurred in an MHC class II restricted fashion. Depletion experiments showed that Langerhans cells (HLA-DR+/CD1a+) were not the principal stimulators of autologous T lymphocytes in the MECLR. These results indicated that mainly HLA-DR+/CD1a- epidermal cells from psoriasis patients could stimulate autologous peripheral blood T lymphocytes in an MHC class II-restricted fashion.

Adult↗

PubMed1991

Differential role of lymphocyte function-associated antigens in the activation of nickel-specific peripheral blood T lymphocytes.

The possible role(s) of the adhesion molecules LFA-1 alpha (CD11a), LFA-1 beta(CD18), ICAM-1 (CD54), CD2 (T11, LFA-2), and LFA-3 (CD58) in the in vitro activation of nickel-specific peripheral blood (PB) T lymphocytes was studied. For this purpose, monoclonal antibodies (MoAb) to these markers were used. Both LFA-2 and LFA-3 appeared to be consistently involved, whereas LFA-1 was inconsistently involved. In studies using antigen-presenting cells (APC) isolated from peripheral blood to present nickel, anti-LFA-1 alpha and/or LFA-1 beta MoAb partially inhibited the in vitro activation of nickel-specific T lymphocytes in nine of 42 patients allergic to nickel. In the other 33 patients variable results, ranging from a slight increase or inhibition of proliferation to no inhibition at all, was observed, in particular when different anti-LFA-1 alpha MoAb were added to the cultures. In those patients who showed no inhibition when anti-LFA-1 (alpha and beta) MoAb were added, no inhibition was also observed when a mixture of anti-LFA-1 (alpha and beta) and ICAM-1 MoAb were added to the cultures. Similar results were also obtained using epidermal APC. In control experiments the various anti-LFA-1 (alpha and beta) MoAb effectively inhibited the tetanus toxoid and Con-A induced T-lymphocyte proliferation as well as the spontaneous aggregation of the JY cell line. Anti-CD2 and anti-LFA-3 MoAb strongly inhibited the proliferative responses of nickel-specific peripheral blood T lymphocytes from all 42 patients. These results indicated that the receptor-ligand interaction between CD2 and LFA-3 is essential for in vitro activation of nickel-specific peripheral blood T lymphocytes. This activation, however, does not regularly involve LFA-1 molecules on T lymphocytes. The involvement of LFA-1 in the activation of nickel-specific T lymphocytes correlated positively with high patch test scores to nickel and the disease activity in contact dermatitis patients.

Adolescent↗

PubMed1991

Regulation of IgE production in mice.

Helper T-lymphocytes tightly regulate the proliferation and antibody production of B-lymphocytes by a variety of molecules called lymphokines. Molecular biology has provided the tools to produce large amounts of these regulatory molecules in highly purified "recombinant" form. Furthermore, monoclonal antibodies have been produced that selectively neutralize each of these lymphokines. This enables thorough investigation of the regulation of human and murine immunoglobulin E (IgE) production. This paper reviews recent data on the regulation of murine IgE production by lymphokines produced by distinct helper T-cell clones. Special attention is paid to the IgE enhancing activity of interleukin-4 (IL-4) and the IgE inhibiting activity of interferon-gamma (IFN-gamma). Evidence is presented that these lymphokines also play a crucial role in genetically determined IgE "high responder" and IgE "low responder" mouse strains.

Animals↗

PubMed1990

Substantially increased sensitivity of the spot-ELISA for the detection of anti-insulin antibody-secreting cells using a capture antibody and enzyme-conjugated insulin.

This paper describes an antibody capture spot-ELISA for the detection of anti-insulin antibody-secreting cells. The assay is based on the binding of secreted antibodies by immobilised isotype-specific capture antibodies and subsequent detection of insulin-specific antibodies with a conjugate of human insulin and alkaline phosphatase (HI-AP). Compared with the conventional approach, using antigen for coating and employing an enzyme-linked detecting antibody, this technique improved the detection of murine cells secreting anti-insulin antibodies of different IgG subclasses.

Animals↗

PubMed1990

The 5T mouse multiple myeloma model: absence of c-myc oncogene rearrangement in early transplant generations.

Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease.

Animals↗

PubMed1990

Interleukin-1 and interleukin-6 in psoriasis.

We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients. Different approaches were pursued. Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay. Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies. Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin. Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta. Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable. Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients. In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced "dot-like" intracellular staining pattern was observed. On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions. Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line. Very low levels of IL-6 mRNA were expressed in KC from psoriasis lesions and healthy individuals. Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA. The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL-1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells. This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales. Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA. dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo.

Blister↗

PubMed1990

Histological and immunohistochemical characterization of joint inflammation and flare-up reactions induced by cloned MT4,Lyt-2-T cells.

This report describes the histological and immunohistochemical characterization of joint inflammations and flare-up reactions in mice induced by cloned MT4+,Lyt-2-T cells. The T-cell clone used was specific for the antigen methylated bovine serum albumin (mBSA) and was inoculated locally into a joint together with the antigen. The histological examination was performed in methylmethacrylate sections, and the various cell types were quantified in distinct regions of the knee joint. The infiltrates consisted predominantly of granulocytes admixed with small numbers of histiocytes. Few lymphocytes were present, while plasma cells were not found. Fibrosis was prominent in the later stages of the inflammation. Immunohistochemical analysis of total unfixed, non-decalcified sections using monoclonal antibodies revealed the presence of T cells which were predominantly of the helper phenotype, sporadic B cells, and a considerable number of Ia-positive cells. Macrophages were scattered throughout the infiltrate. The synovial lining was shown to express Ia antigens and to contain cells that stained with macrophage markers. Cell clusters were found including helper T (Th) cells, some B cells, and Ia-positive cells. These results are in line with immunohistological examinations in other arthritis models and resemble the early events in human rheumatoid arthritis. The data indicate that activated helper T cells are required and sufficient to give rise to the inflammatory infiltrates that are characteristic of the inflammations and exacerbations in human rheumatoid arthritis.

Animals↗

PubMed1990

Effects of Acid stress on aerobic decomposition of algal and aquatic macrophyte detritus: direct comparison in a radiocarbon assay.

Radiolabeled phytoplankton and macrophyte lignocelluloses were incubated at pHs 4 and 7 in water from a naturally acidic freshwater wetland (Okefenokee Swamp; ambient pH, 3.8 to 4.2), a freshwater reservoir (L-Lake; pH 6.7 to 7.2), and a marine marsh (Sapelo Island; pH approximately 7.8). The data suggest that acidity is an important factor in explaining the lower decomposition rates of algae in Okefenokee Swamp water relative to L-Lake or Sapelo Island water. The decomposition of algal substrate was less sensitive to low pH ( approximately 5 to 35% inhibition) than was the decomposition of lignocellulose ( approximately 30 to 70% inhibition). These substrate-dependent differences were greater and more consistent in salt marsh than in L-lake incubations. In both freshwater sites, the extent to which decomposition was suppressed by acidity was greater for green algal substrate than for mixed diatom or blue-green algal (cyanobacteria) substrates. The use of different bases to adjust pH or incubation in a defined saltwater medium had no significant effect on substrate-dependent differences. Although pH differences with lignocellulose were larger in marine incubations, amendment of lakewater with marine bacteria or with calcium, known to stabilize exoenzymes in soils, did not magnify the sensitivity of decomposition to acid stress.

Journal Article↗

PubMed1990

Amplification of the c-myc and the pvt-like region in human multiple myeloma.

Genetic alterations that lead to the clonal expansion of differentiated cells in multiple myeloma have still to be elucidated. Many chromosomal aberrations have been found, but until now, none of them is typically associated with multiple myeloma. In search for genetic defects in multiple myeloma we studied the structure and expression of the c-myc oncogene and the pvt-like region because of their frequent association with other B-cell malignancies. Here we report co-amplification of the c-myc oncogene and the 5' part of the pvt-like region in two out of 26 cases of multiple myeloma. In both cases only kappa-light chains were produced. The amplification also manifested itself at the RNA level. Total RNA was analysed in one of these two cases showing abundant c-myc mRNA. In the same RNA sample we also detected a strong hybridizing band of about 7 kb, when the pSS.4 probe, representing the 5' part of the pvt-like region, was used. This band was not present in total RNA from normal bone marrow cells or bone marrow from multiple myeloma patients without the amplification of c-myc and the pvt-like region. Until now, transcripts of the pvt-like region were only found in a few human cell lines ranging in size from 1 to 11 kb. This is the first case in which a high expression of a +/- 7 kb transcript of the pvt-like region has been found in freshly obtained tumor material probably due to a pvt-amplification. The occurrence of abnormalities in the c-myc and the pvt-like region in multiple myeloma is a rare event and may be associated with the progression of this type of tumor.

DNA, Neoplasm↗