PubMed Health⌕ Search

Biomedical subjects

R Huss

Publications and source records attributed to R Huss.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Immunogenic hyperthyroidism with hyperdynamic heart failure and early cirrhotic transformation of the liver].

HISTORY AND CLINICAL FINDINGS: A 58-year-old woman was admitted because of jaundice, ascites and marked oedema. For three years she had suffered from nervousness, decreasing fitness and weight loss, which had been assumed as due to chronic alcoholism. Liver biopsy revealed extensive fibrosis, in part with early cirrhotic transformation. This was followed by cardiac failure with atrial fibrillation (ventricular rate 140/min) and marked pleural effusions. The thyroid was diffusely enlarged and there were signs of exophthalmos. INVESTIGATIONS: Bilirubin concentration was 3 mg/dl, lactate dehydrogenase activity was 310 U/l, cholesterase 1.3 kU/l and the prothrombin test was 21%. The TSH level was 0.01 microU/ml while the free thyroxine level was 4.7 ng/dl and that of free triiodothyronine 13.5 pg/ml. Chest radiograph revealed cardiomegaly, bilateral peripheral pulmonary congestion and pleural effusions to midfield. Right heart catheterization excluded pulmonary hypertension; cardiac output was 10l/min. The thyroid was enlarged on ultrasound and diffusely echopoor, as in immune thyroid disease. TREATMENT AND COURSE: Cardiac failure regressed and thyroid function normalized within ten days on propranolol, 4 x 40 mg and thiamazole 3 x 40 mg daily intravenously. Subtotal thyroidectomy was performed three weeks later with subsequent thyroid hormone substitution. Liver functions were normal six months later and ultrasound showed no signs of cirrhotic change and the ascites had resolved. CONCLUSION: Hyperthyroidism is frequently associated with changes in liver functions. In extreme cases, high-output cardiac failure may occur, with liver congestion and clinical as well as histological changes like those in liver cirrhosis.

Adrenergic beta-Antagonists↗
PubMed1997

In vivo radioprotective effect of AcSDKP on canine myelopoiesis.

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) interferes with G1/S-phase progression, and the resulting cell cycle arrest is thought to protect hematopoietic stem cells against injury by cycle-active cytotoxic agents. We investigated the radioprotective effect of AcSDKP in a canine radiation model. Dogs were given total-body irradiation (TBI) at an exposure rate of 10 cGy/min, either without further therapy (control) or with administration of AcSDKP at 0.05-500 micrograms/ kg/24 h beginning before and continuing until after completion of TBI. At 400 cGy of TBI, one of 28 control dogs and one of eight AcSDKP-treated dogs recovered hematopoiesis (p = 0.40). At 300 cGy, seven of 21 control dogs recovered hematopoiesis compared with five of five AcSDKP-treated dogs (p = 0.01). In dogs given 300 cGy and AcSDKP, the granulocyte nadirs were less profound (p = 0.04) and occurred later (p = 0.04) than among controls; platelet kinetics did not differ. These data suggest, therefore, that AcSDKP provides a radioprotective effect in dogs exposed to 300 cGy TBI. Such an effect might be beneficial in recipients of intensive radiation therapy. Conceivably, the effect on hematopoietic recovery could be amplified by growth factor administration after irradiation.

Animals↗
PubMed1997

Functional and ultrastructural studies on the burst of c-kit ligand containing secretory cytoplasmatic vesicles.

A fibroblast-like cell line (D064) was established from canine marrow long-term cultures. These cells start to differentiate into hematopoietic progenitor precursors under the influence of c-kit ligand, functioning in an autocrine and paracrine fashion. The message for c-kit ligand is transcribed in the fibroblast-like cell line and the ligand for the tyrosine-kinase c-kit is expressed on the cell surface as well as secreted in its soluble form. With a monoclonal antibody directed against all isoforms of c-kit ligand, the expression of c-kit ligand was investigated functionally and topographically by electron microscopy. Ultrastructural analysis revealed c-kit ligand in electron dense vesicles which were transported to the cell surface and burst to release the soluble, non-membrane bound isoform of c-kit ligand. A membrane bound isoform of c-kit ligand was also present on the cell membrane.

Animals↗
PubMed1997

Haematopoietic progenitor cells transfected with a differentiation antigen show cellular transformation and tumour growth in mice.

A stromal cell line, D064, derived from canine bone marrow stroma, was established and differentiates into haematopoietic progenitors under the influence of growth factor signalling. While differentiating, these cells start to express MHC class II molecules (HLA-DR homologues) on their surface. The transfection of these fibroblast-like cells with retroviral constructs containing the canine MHC class II DR-genes (DRA and DRB) induces a change in morphology, alteration of cell cycle progression and tumour formation in nude mice. Transfected cells are smaller than untransfected parental cells and do not require adherence (anchorage dependent growth). The doubling time of untransfected cells was reduced by more than half, as a sign of accelerated cell cycle progression. Injected subcutaneously into nude mice the DR+ transfected cells formed solid tumours, while untransfected cells showed no sign of tumour formation. The transfection-induced changes were seen only with constructs carrying the open reading frame of DRA plus DRB in the correct orientation and expressing the complete DR-dimer on the cell surface. Constructs with DRA and DRB in reverse orientation or vectors without any insert did not differ from the parental cells. These observations suggest that mechanisms normally controlling cell cycle and differentiation can be disrupted by the constitutive transcription and expression of differentiation antigens.

Animals↗
PubMed1997

Intrathymic maturation of CD4+ T-lymphocytes in an MHC class II deficient transplant model.

Major histocompatibility complex (MHC) class II knockout (class II-) mice fail to generate CD4+ CD8- T-lymphocytes. We were interested in determining whether these class II- mice could be reconstituted with CD4+ CD8- T-lymphocytes following marrow transplantation from normal (class II+) donors. Transplantation of class II+ marrow into lethally irradiated class II- recipients failed to generate peripheral CD4+ CD8- T-lymphocytes. Unexpectedly, however, transplantation of class II marrow into class II+ recipients also resulted in a deficiency of CD4+ CD8- cells. Analysis of intrathymic T cells showed normal distribution of CD4 and CD8 single and double positive or negative thymocytes in normal recipients, while class II- recipients always lacked CD4+ CD8- T cells intrathymically. These results suggest, therefore, that T-cell maturation in mice requires the presence of MHC class II antigens not only in the thymus but also on immature, marrow-derived pre-thymocytes.

Animals↗
PubMed1997

Blindness and visual impairment in a region endemic for onchocerciasis in the Central African Republic.

AIMS: A population based survey of blindness and visual impairment was conducted in the district of Bossangoa, Central African Republic. METHODS: A total of 48 communities were randomly selected, and 6086 people examined. RESULTS: The prevalence of blindness (visual acuity in the better eye less than 3/60) was 2.2%, and visual impairment 3.0% (6/24 to 3/60 in the better eye). The major causes of blindness were onchocerciasis (73.1%), cataract (16.4%), trachoma (4.5%), and glaucoma (2.2%). CONCLUSION: Around 95.5% of all blindness could potentially have been prevented or treated. Ivermectin mass distribution is hoped to prevent 50% of all forms of visual loss in the future.

Adolescent↗
PubMed1997

New definition and methods for isolation of the earliest peripheral blood-derived hematopoietic stem cells.

Peripheral blood contains transplantable pluripotent hematopoietic progenitor cells, which are defined by the expression of certain surface antigens, such as CD34, and the absence of lineage-specific markers (lin-). Here we describe CD34- DR- adherent growing hematopoietic progenitor precursors which were separated and isolated from peripheral blood by interleukin 6(IL-6)-mediated plastic adherence. These peripheral blood mononuclear cells attach to the plastic surface of tissue culture flasks in the presence of human recombinant IL-6 and assume fibroblast-like morphology. These adherent cells are CD34- and HLA-DR-, and respond to various growth factors with the expression of surface antigens, changes in morphology and the expression of cell cycle-controlling kinases. Stem cell factor induces differentiation of the CD34- DR- adherent cells to become nonadherent and to differentiate into CD34+, and eventually HLA-DR+ cells, and produce colony-forming units (CFU) in semi-solid agar. While IL-6 conveys adherence of these cells, the addition of stem cell factor induces differentiation into nonadherent cells. Our observations suggest the possibility of isolating a true hematopoietic stem cell before the level of CD34 and HLA-DR expression.

Antigens, CD34↗
PubMed1996

Neutralization of stem cell factor in vitro and in vivo: dose-dependent inhibition of stromal cells and induction of granulocyte/monocyte differentiation.

Stem cell factor (SCF), also termed mast cell growth factor or c-kit ligand, plays a central role in the regulation of hematopoiesis and maintenance of viability of hematopoietic cells. We used a new murine monoclonal antibody (MAb) specific for canine SCF to further dissect the role of SCF in vitro and in vivo. This neutralizing MAb, RG7.6 (IgG1), recognizes the soluble form as well as the membrane-bound form of SCF on marrow-derived stromal cells. Treatment of long-term bone marrow cultures (LTMC) with RG7.6 suppressed or stimulated the production of CFU-GM, depending on the MAb concentration and the time of addition to cultures. At concentrations of 0.1-10 micrograms/ml given on the day of recharge of the LTMC, RG7.6 resulted in sustained suppression of CFU-GM grown from nonadherent cells. In contrast, higher doses of RG7.6 (20-100 micrograms/ml) led to a two- to threefold increase in CFU-GM formation from nonadherent cells after 3 days of RG7.6 exposure; after longer RG7.6 exposure there was a rapid decline in the number of CFU-GM. The early increase of CFU-GM was even more distinct when RG7.6 addition to LTMCs was delayed until 1 day before cells were plated for the CFU-GM assay. The early increase of CFU-GMs in the presence of high-dose RG7.6 was mimicked by the addition of granulocyte colony-stimulating factor (G-CSF) to cultures containing suboptimal concentrations of RG7.6, suggesting the possibility that the "positive" response to high-dose RG7.6 was due to an overriding effect of other growth factors, e.g., G-CSF. In stromal cells expressing the membrane-bound form of SCF, the presence of MAb RG7.6, even at low concentrations, interfered with thymidine uptake and proliferation. RG7.6 was also tested in vivo. RG7.6 was given intravenously immediately (days 0-4) after total body irradiation and autologous bone marrow transplantation, and granulocyte counts were followed. The post-irradiation nadir of peripheral blood granulocytes was indistinguishable from controls at low doses of RG7.6 but became more shallow as higher doses of RG7.6 were infused, again suggesting a positive effect on granulocyte differentiation. Thus, the SCF-specific MAb appears to interfere with both stromal and hematopoietic cell function. While only inhibition was observed at lower concentrations, a transient increase in granulocyte production was seen at higher MAb concentrations.

Animals↗
PubMed1996

Facilitation of DLA-incompatible marrow grafts by donor-specific serum transferrin?

Studies in mice have shown that donor-specific plasma transferrin (TF) given to the recipient in the peritransplant period facilitates engraftment of marrow from histoincompatible donors. Dogs given 920 cGy of total body irradiation (TBI) and infused with marrow from an unrelated major histocompatibility complex (DLA) different donor generally fail to engraft; only approximately 20% of dogs achieve sustained engraftment. We have now investigated in this model whether the infusion of donor-specific plasma TF would facilitate engraftment. Ten dogs were given TBI, followed at 23 h by an intravenous dose of TF, at 24 h by marrow from the same donor, and another dose of TF at 48 h; six dogs also received postgrafting methotrexate (MTX). Seven dogs (three of four without MTX, four of six with MTX) had sustained engraftment, and three dogs failed to engraft. A single dog given third-party TF failed to engraft. Among five dogs not given TF two achieved sustained engraftment. This pilot study suggests that donor-specific TF facilitates engraftment of DLA-incompatible marrow. Further studies are warranted.

Animals↗
PubMed1996

Applications of hematopoietic stem cells and gene transfer.

OBJECTIVE: In this review, the hematopoietic stem cell is defined and the change of this definition over the past decades is elucidated. Besides we discuss how the applications of stem cell transplantation have changed in the same period of time. In addition to the biology of hematopoietic stem cells, the most recent applications in gene transfer and gene therapy will be discussed. DATA SOURCES: Review of the literature and results of studies performed at the Fred Hutchison Cancer Research Center in Seattle, USA. SELECTION CRITERIA: Peer review journals and papers relevant to the topic. RESULTS: Based on the initial radiation experiments in mice, the hematopoietic stem cell was defined by its biological properties and later by the expression of certain surface antigens, as well as the absence of lineage-specific markers. Quite recently, more and more evidence has emerged that hematopoietic stem cells can be isolated from peripheral blood and that there might be a common progenitor of hematopoiesis and the marrow microenvironment. Hematopoietic stem cells are also a useful aid for gene therapy in a broader range of immunodeficiencies and metabolic disorders. CONCLUSIONS: Peripheral blood stem cells transplantation and gene therapy will be useful tools to treat a broader spectrum of diseases using uncommitted very early progenitor cells isolated from peripheral blood.

Animals↗
PubMed1996

Tacrolimus (FK506) and methotrexate regimens to prevent graft-versus-host disease after unrelated dog leukocyte antigen (DLA) nonidentical marrow transplantation.

We previously reported an synergism between methotrexate and tacrolimus (FK506) in preventing graft-versus-host disease (GVHD) in dogs given DLA-nonidentical unrelated marrow grafts after 9.2 Gy of total body irradiation (TBI). Methotrexate was given at 0.4 mg/kg i.v. on days 1, 3, 6 and 11 and FK506 at 0.15 mg/kg/day i.m. on days 0-8 and 0.5 mg/kg/day orally on days 9-90. Half of the dogs became long-term survivors. A major toxicity was gastrointestinal, and 25% of dogs died with intussusception. The current study addresses the problem of intussusception by making changes in drug doses used. In one group of dogs, FK506 was reduced to 0.075 mg/kg i.m. on days 1-8, while methotrexate was administered per original schedule. In a second group, methotrexate was reduced to a single dose on day 7, while FK506 was either administered per the original or reduced-dose schedule. None of the 17 current dogs developed intussusception, however, all but two dogs died with GVHD (n = 12) or graft failure (n = 3). Only two dogs survived after transient GVHD. Results show that there is little room for maneuvering FK506 or methotrexate doses, and hopes of reducing gastrointestinal toxicity by dose modifications while retaining the ability to prevent GVHD were not fulfilled.

Animals↗
PubMed1996

Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia.

The association of mixed (donor/host) chimerism with graft-versus-host disease (GVHD), graft rejection, disease recurrence and survival was investigated in 116 patients with aplastic anemia and 197 patients with chronic myelogenous leukemia (CML) transplanted with unmodified marrow from an HLA-identical sibling donor of opposite sex. Patients with aplastic anemia were conditioned with cyclophosphamide (CY), patients with CML were conditioned with a combination of CY and total body irradiation (TBI) or busulfan. Sixty-three of the patients with aplastic anemia (54%) and 100 patients with CML (51%) were categorized as mixed chimeras based on the concurrent presence of donor and host lymphohematopoietic cells 14 days or later after transplantation. The TBI dose used for conditioning was inversely correlated with the development of mixed chimerism (P < 0.0001) among CML patients. No other patient- or transplant-related parameter was identified which contributed significantly to the development of mixed chimerism. The incidence of rejection was higher but not significantly so in patients with aplastic anemia who were mixed chimeras. The incidence of leukemic relapse in patients with CML who were mixed chimeras was increased only if mixed chimerism occurred after day 100 (P = 0.015). The incidence of acute GVHD (grades II-IV) was lower in mixed chimeras than in complete chimeras, but this difference was statistically significant only for patients with aplastic anemia given single-agent GVHD prophylaxis (P = 0.0008). Mixed chimeras in that group also had a better survival than complete chimeras, while no significant difference was observed in patients with aplastic anemia given drug combinations for GVHD prophylaxis. Among patients with CML, both overall survival (P = 0.03) and relapse-free survival (P = 0.04) were significantly superior in mixed than in complete chimeras. Thus, mixed chimerism was frequent among patients with aplastic anemia and with CML and was not uniformly associated with graft failure or leukemic relapse. The interaction between conditioning regimen, GVHD prophylaxis and chimerism are complex. The survival advantage of mixed chimeras is only in part related to a lower incidence of GVHD and other factors are likely to contribute.

Adolescent↗
PubMed1996

Delay of radiation-induced decline and recovery of hematopoiesis following treatment with anti-HLA-DR antibody.

A dose of 200 cGy of total-body irradiation (TBI) is nonlethal in dogs: Following a granulocyte nadir in the third week post-TBI, peripheral blood cell counts recover to normal values by about 5 weeks. In the context of studies on a potential role of major histocompatibility (MHC) class II antigens in the regulation of stress hematopoiesis, we tested the effect of anti-MHC class II monoclonal antibodies (mAbs) on hematologic recovery after TBI. Thirteen dogs were given 200 cGy of TBI not followed by marrow infusion. Five received no additional treatment (concurrent controls) and eight were given daily intravenous (IV) injections of anti-class II mAbs H81.9 (anti-HLA-DR; n = 6) or B1F6 (anti-HLA-DR and -DP; n = 2) at 0.6 (n = 4) or 1.2 mg/kg/d (n = 4) on days 0-4 (n = 7) or days 0-9 (n = 1). One control dog died early from an intercurrent infection and four recovered uneventfully. Dogs given mAbs after TBI showed significantly different granulocyte and platelet kinetics. The granulocyte nadir was lower (p = 0.09) and was reached later (p = 0.005), the duration of neutropenia was longer (p = 0.08), and recovery occurred later (p = 0.02) than among controls. Similarly the platelet nadir was lower (p = 0.05), thrombocytopenia lasted longer (p = 0.02), and recovery occurred later (p = 0.02) than among controls. Four of eight mAb-treated dogs died with marrow aplasia. We propose that following irradiation, HLA-DR mediated signals result in terminal differentiation in more mature hematopoietic precursors but interfere with replication or differentiation in early hematopoietic precursors. These observations suggest a role for MHC class II molecules in the regulation of stress hematopoiesis.

Animals↗
PubMed1995

Major histocompatibility complex class II-mediated inhibition of hematopoiesis in long-term marrow cultures involves apoptosis and is prevented by c-kit ligand.

Expression of major histocompatibility complex (MHC) class II molecules is developmentally regulated and lineage dependent. Their role in hematopoiesis is not well defined. Previous studies in a canine model showed that dogs given 920 cGy of total body irradiation, transplanted with autologous marrow, and treated with anti-MHC class II monoclonal antibody (MoAb) immediately posttransplant experienced only a transient granulocyte recovery that was followed by graft failure. In the present study, the effect of anti-MHC class II MoAbs on canine in vitro hematopoiesis was investigated. Anti-MHC class II MoAb H81.9 or B1F6 (both recognizing nonpolymorphic determinants) had no inhibitory effect when added directly to colony-forming unit-granulocyte-macrophage (CFU-GM) grown in agar. However, the addition of intact MoAb or as F(ab')2 fragments to long-term marrow cultures (LTMCs) resulted in a dose-dependent inhibition of the generation of CFU-GM among nonadherent cells. Inhibition was most profound with MoAb added at the time of initiation of culture. However, even if MoAb was added 3 weeks after recharging LTMCs, CFU-GM generation rapidly decreased. In addition, the number of adherent cells in LTMCs decreased; predominantly fibroblast-like cells with prominent cytoplasmic vesiculation remained. Acridine orange/ethidium bromide staining and TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) tests showed an increase in the proportion of apoptotic cells in both the nonadherent and adherent compartments. Binding of anti-MHC class II MoAb to unfractionated marrow cells resulted in an increase in free (Ca2+)i; no changes in tyrosine phosphorylation pattern were observed. The addition of stem cell factor (SCF), but not granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, to LTMCs prevented apoptosis, and the generation of CFU-GM was indistinguishable from controls. Similarly, a supportive adherent layer was maintained. Thus, anti-MHC class II MoAbs interfere with hematopoiesis both in vitro and in vivo. The mechanism involves programmed cell death in subpopulations of adherent and nonadherent cells. Inhibition of hematopoiesis is abrogated by exogenous SCF.

Animals↗
PubMed1995

Contact- and growth factor-dependent survival in a canine marrow-derived stromal cell line.

Cell-cell interactions and the presence of growth factors such as stem cell factor (SCF; or c-kit ligand) or interleukin-6 (IL-6) are involved in the proliferation and differentiation of the canine marrow-derived stromal cell line DO64. In the presence of SCF, stromal cells are induced to differentiate, but not to proliferate. In contrast, in the presence of IL-6, stromal cells are induced to proliferate rather than to differentiate in culture. Both SCF and IL-6 are produced by the stromal cells themselves and, thus, act as autocrine factors. In addition, DO64 cells also interact physically with each other in culture when grown under optimal culture conditions (70% to 90% cell confluence and in the presence of serum), thereby supporting proliferation and maintaining viability. Under conditions of lower cell density or low serum or growth factor concentrations in culture, DO64 cells tend to aggregate and form clusters. This increase in local cell concentration is associated with preservation of viability, presumably because of the accumulation of autocrine factors. If no signal, neither intercellular nor soluble, is provided, and DO64 cells are not able to reach a critical cell density or to produce sufficient factors in an autocrine fashion, the cells cease to proliferate and eventually die.

Animals↗