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Biomedical subjects

R Huss

Publications and source records attributed to R Huss.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differentiation of canine bone marrow cells with hemopoietic characteristics from an adherent stromal cell precursor.

Stromal cell lines were established from canine long-term marrow cultures, cloned by limiting dilution, and maintained in stromal cell-conditioned medium. These cells grew adherent, maintained stable growth rate and morphology under standard conditions (in 20-30% conditioned medium; confluency, 70-90%), and supported hemopoiesis in long-term marrow cultures. In the presence of exogenous recombinant canine stem cell factor (rcSCF), round cells developed from the adherent layer, detached, and remained in culture as viable floating cells. Round floating cells also appeared when cultures were grown to > 90% confluency without rcSCF. Round cells were smaller than adherent cells, expressed CD34, showed basophilic plasma, and stained positive for c-kit, MHC-class II markers, and myeloid markers. In standard assays for colony formation, the detached cells produced granulocyte-macrophage colony-forming units (CFU-GM), fibroblast colony-forming units (CFU-F), and less well-defined colony-forming units. In addition, on allogeneic feeder cells in long-term cultures, these cells generated hemopoietic colonies. Strikingly, the differentiation was reversible: when nonadherent cells were resuspended at lower density in serum-containing medium, they reattached and grew to confluence when, once again, round cells detached. Detached cells from this secondary cycle produced mainly CFU-F and few CFU-GM when placed in clonal assays. These results suggest that some fibroblast-like stromal cells have the potential to differentiate into cells with hemopoietic characteristics. These observations provide evidence for the existence of a quiescent precursor of hemopoietic progenitors in the bone marrow stroma of the adult dog.

Animals↗
PubMed1995

Stem cell factor-induced expression of p27kip-1 during hematopoietic differentiation.

The canine marrow stroma-derived CD34- DR- cell line D064 is able to differentiate into cells with characteristics of hematopoietic progenitors. While differentiating, these cells start to express CD34 and DR. Differentiation is induced by stem cell factor (SCF), while interleukin-6 (IL-6) inhibits differentiation, but promotes proliferation. The influence of SCF and IL-6 on differentiation and proliferation is reflected in the expression of p27kip-1. SCF induces a transient expression of p27kip-1, while no p27kip-1 is detectable in the presence of IL-6 or an anti-SCF monoclonal antibody. The accumulation of intracellular p27kip-1 precedes the differentiation of D064 cells. As these cells start to proliferate and more committed progenitors emerge, p27kip-1 is no longer expressed.

Animals↗
PubMed1995

Cyclosporine-induced apoptosis in CD4+ T lymphocytes and computer-simulated analysis: modeling a treatment scenario for HIV infection.

Cyclosporine A (CsA) is a potent immunosuppressive drug which interferes in vitro and in vivo with T-cell function. CsA has been shown to arrest T-cell maturation intrathymically and to inhibit T-cell proliferation. In this study, we demonstrate that CsA induces apoptosis in the canine CD4+ CD8- T-lymphocyte cell line 401 in a dose- and time-dependent fashion. Similar results could also be obtained from human peripheral blood lymphocytes. Apoptosis is observed within 4 hours after CsA application and is not prevented by excessive addition of ConA supernatant as a source of interleukins. The induction of apoptosis in CD4+ T lymphocytes suggests a possible treatment option for human immunodeficiency virus (HIV) infections, since the major target population for the HIV would be ablated at short term. A computer-simulated analysis with the "Cybermouse" HIV model confirmed that the virus would eventually disappear and HIV-infected macrophages would also be substantially reduced if CsA were given in combination with drugs which block viral replication (3'-azido 3'-deoxythymidine or 2',3'-dideoxycytidine). This treatment scenario could be applied under controlled conditions and with supportive patient care. A further review of the literature also suggests the positive impact of CsA treatment on the progression and outcome of AIDS-related mortality.

Animals↗
PubMed1995

Ultrastructural localization of stem cell factor in canine marrow-derived stromal cells.

Stromal cell lines derived from canine long-term bone marrow cultures (LTBMC) were characterized regarding the expression of growth factors and especially the localization of stem cell factor (SCF) (c-kit ligand). One cell line (DO64) was immortalized by transformation with a retroviral vector containing the open reading frames (ORFs) E6 and E7 of the human papilloma virus type 16 (HPV-16). Transfection did not change cellular characteristics but rendered the cell line more independent from culture conditions. The transformed line DO64 consisted mainly of fibroblast-like cells. In addition, some cells showed endothelial and some smooth-muscle cell features. Stromal cells expressed a broad spectrum of surface markers, including low levels of major histocompatibility-complex (MHC) class-II antigens. A new murine monoclonal antibody (MAb), RG7.6 (IgG1), specific for canine SCF, recognized the majority of fibroblast-like stromal cells. The staining pattern for SCF showed perinuclear and intracytoplasmic dense areas. Immunoelectron microscopy revealed the localization of SCF in secretory vesicles, the perivesicular cytoplasm, and bound to the cytoplasmatic membrane. RNA analysis showed that stromal cells transcribed, in addition to SCF, messages for granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte CSF (GM-CSF), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). In summary, we have established and characterized canine marrow-derived stromal cell lines, and using the new MAb RG7.6, we have localized SCF to cytoplasmatic vesicles as well as the membrane of stromal cells.

Animals↗
PubMed1994

Major histocompatibility complex class II expression is required for posttransplant immunological but not hemopoietic reconstitution in mice.

We had previously shown in a canine model that the administration of anti-MHC class II monoclonal antibody (MAB) immediately after autologous marrow transplantation prevented hemopoietic reconstitution. Since MHC class II expression in mice differs from that in dogs we were interested in determining the effect of MHC class II manipulation on posttransplant hemopoietic and immunological recovery in mice. Three murine models including MHC class II knock-out mice were studied. BALB/c mice (I-E+, I-A+) given anti-MHC class II MAB H81.9 (anti-I-E; 1 mg/kg/day, days 0-4) after TBI and infusion of syngeneic marrow or infused with anti-I-E purged marrow both showed normal hemopoietic reconstitution. Similarly, C57B1/6 mice (I-E-, I-A+) transplanted with M5/114 (anti-I-A) purged marrow recovered normal hemopoiesis. MHC class II knock-out (C2D) mice, which lack class II completely, also recovered normal hemopoiesis after TBI and transplantation with either normal or class II-deficient (C2D) marrow, although the kinetics of platelet recovery as determined by megakaryocytopoiesis and platelet counts on day 14 were slightly delayed. C57B1/6 mice transplanted with C2D marrow recovered normally. Immunologic recovery, however, was abnormal both in C2D recipients and in normal mice transplanted with C2D marrow: While CD8+ T lymphocytes recovered normally, no (or only very few) CD4+ T cells were identified posttransplant. Treatment of normal mice with anti-MHC class II MAB in vivo or transplantation of MHC class II-purged marrow, however, did not interfere with complete immunological recovery, although T cell maturation was slightly delayed. Thus, complete immunological reconstitution requires the expression of MHC class II on marrow-derived precursor cells, while the expression of MHC class II antigens is not a requirement for hemopoietic reconstitution in mice.

Animals↗
PubMed1994

Rescue from anti-MHC class II antibody-mediated marrow graft failure by c-kit ligand.

Dogs given 920 cGy of total body irradiation (TBI) followed by autologous marrow infusion uniformly achieve sustained hematopoietic reconstitution. We have previously shown that administration of the anti-MHC class II monoclonal antibody (MoAb) H81.98.21 (IgG2a) at 0.6 mg/kg/d immediately after transplantation results in delayed graft failure. A second noncrossblocking anti-MHC class II MoAb, B1F6, of the same isotype, at the same dose, did not interfere with sustained engraftment, suggesting that the observed effect was epitope dependent. Although higher concentrations of B1F6 were required, in the present study both MoAbs interfered with the propagation of long-term marrow cultures. When MoAb B1F6 was given in vivo at 1.2 mg/kg/d, ie, twice the dose used previously, dogs so treated also developed delayed marrow graft failure. Marrow failure with either MoAb involved myeloid, erythroid, and megakaryocytic lineages. Administration of recombinant canine c-kit ligand/stem cell factor (SCF) for 7 or 21 days posttransplant resulted in reversal of graft failure. Although the short course did induce a broad transient early peak of granulocytes, the longer course of SCF was accompanied by earlier sustained recovery than the short course. In conclusion, therefore, marrow graft failure induced by anti-MHC class II MoAb does not appear to be epitope dependent, involves all hematopoietic lineages, and is overcome by the administration of c-kit ligand.

Animals↗
PubMed1993

In vitro determination of self-reactivity in the early postcyclosporine period.

Since cyclosporine A(CsA) was introduced into transplantation medicine to prevent graft-versus-host disease (GvHD) as well as graft rejection, side-effects became obvious. When CsA is given and withdrawn GvHD-like symptoms can occur even in an autologous setting. To understand this mechanism we tested the allo- and self-reactivity of murine spleen lymphocytes in an in vitro assay. Mice of four different strains with two distinct MHC class I backgrounds (H-2d and H-2k) were treated with 60 mg/kg/day CsA intraperiteonally for ten days. In an attempt to examine the possibility that the CsA-induced autoimmunity requires the presence of the thymus, half of these four- to six-week-old mice were also thymectomized prior to the CsA treatment. Within one day after CsA was stopped, all mice that received CsA during treatment showed reactivity against self-MHC-bearing spleen cells. This was demonstrated in a primary in vitro stimulation assay followed by a chromium-release assay (H-2d-anti-H-2d and H-2k-anti-H-2k). However, alloreactivity (H-2d-anti-H-2k and H-2k-anti-H-2d) was suppressed. At this point in time, no natural killer (NK) activity was detectable in any of the CsA-treated mice. Ten days after stopping CsA, the autoreactivity was no longer detectable in any mouse strain, whether thymectomized or not, whereas the alloreactivity and the NK activity finally recovered. The in vitro phenomena of self-reactivity, which occurred between day one and day 10 after CsA withdrawal, could be adoptively transferred from syngeneic in vitro reactive T cell populations into H-2 identical mice. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Major histocompatibility complex class II molecules, hemopoiesis and the marrow microenvironment.

Currently available data indicate that the earliest identifiable hemopoietic progenitor in normal marrow is CD34+ MHC class II-; subsequent expression of MHC class II antigens is maturation and lineage dependent. Studies on embryonal cells suggest that CD34+DR- cells are actually the common precursors for stromal and hemopoietic elements, with the earliest hemopoietic precursor being CD34+DR+. DQ antigens are apparently not expressed in cells of hemopoietic potential and the expression of DQ appears to be regulated differentially from DR and DP. MHC class II antigens are also expressed on some stromal cells, especially those with endothelial and macrophage features. MHC class II molecules are involved in hemopoietic cell/stroma interaction. The presence of anti-MHC class II monoclonal antibodies (MABs) at early stages of stem cell proliferation/differentiation, at least under conditions of marrow stress, induces signals which may result in final, especially granulocytic, differentiation of later precursors. These may interfere with the survival of those cells which are required for long-term hemopoietic reconstitution. Observations in allogeneic marrow transplant recipients support a role of MHC molecules as expected in allogeneic interactions. Results in autologous models point towards a role of MHC class II molecules other than that of a histocompatibility marker insofar as these molecules or signals transmitted by them appear to be involved in the regulation of hemopoiesis.

Bone Marrow↗
PubMed1992

[Antiviral drug therapy of infections caused by Herpes simplex and Varicella Zoster viruses].

Herpes simplex virus type 1 and 2 may cause painful mucocutaneous lesions in both immunosuppressed and immunocompetent patients. Indications for the use of acyclovir (ACV) are reviewed. In the second part the management of infections caused by varicella-zoster virus are discussed. Primary varicella (chickenpox) in immunosuppressed children should be treated with i.v. ACV without delay. In healthy patients varicella pneumonia needs to be treated with ACV. Healthy patients with herpes zoster are not usually candidates for antiviral therapy. The only exception is herpes zoster ophthalmicus. In patients with severe immunosuppression, such as transplant recipients, ACV therapy is recommended in order to reduce the rate of dissemination. First reports and our own observations on the development of ACV-resistant HSV and VZV isolates stress the importance of discriminating use of ACV and other antiviral compounds in immunosuppressed patients.

Acyclovir↗
PubMed1992

Herpes zoster as an indicator of HIV infection in Africa.

In areas where resources for health information are limited, the incidence of herpes zoster can usefully be monitored as an indicator of HIV infection. A sudden parallel rise of the number of symptomatic HIV cases and herpes zoster cases was observed in a northern district of Zimbabwe. Herpes zoster was made locally reportable. Three years later the incidence of herpes zoster and HIV in the hospital and of herpes zoster in the surrounding rural health centres was analysed. The herpes zoster attack rate and the HIV seropositivity rate of herpes zoster patients resembled those elsewhere in Africa. The distribution of cases of zoster was comparable with that of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pattern of HIV-infection in Hurungwe district, Mashonaland West, Zimbabwe.

After the first case of HIV-infection had been diagnosed in 1986 in a Northern district of Zimbabwe, a local hospital based surveillance system, was introduced. In order to monitor the spread of the epidemic in the district, residence, age, sex and clinical presentation of all newly diagnosed HIV-patients were recorded. After three years, the data were compiled and analysed with the following results. Altogether 887 symptomatic HIV-patients (0.5 pc of the district population) were diagnosed. The most common HIV-associated signs and symptoms were PGL (47 pc), chest infection (29 pc), herpes zoster (24 pc) and chronic STDs (15 pc). The female-to-male ratio in adults was 1.4. The average age on diagnosis in women was 26.0 +/- 6.7 years and in men 30.7 +/- 8.6 years. The three years' cumulative incidence of HIV-cases was 27.2/1,000 in the urban area and 3/1,000 in the rural areas of the district.

Adolescent↗
PubMed1992

Tracheal papilloma presenting as asthma in a child.

This report describes a child with a tracheal papilloma who was initially diagnosed and treated as having asthma. The case illustrates that all wheezing in children should not be attributed to asthma.

Bronchoscopy↗
PubMed1991

[Hypertension in the old age: how to treat it?].

Therapeutic agents for the treatment of hypertension in the elderly are the well known basic antihypertensive drugs (Diuretics, beta-blocking agents, calcium antagonists and ACE-inhibitors). Choice is determined by concomittant diseases increasing with age. In the elderly patient the assessment of benefit and risk is particularly essential. Drugs should therefore not be installed without exact information of the patient and be started at the smallest possible dose. If tolerance is good the dose may be raised of prescription of an additional drug be evaluated cautiously.

Adrenergic beta-Antagonists↗
PubMed1991

[Hypertension in the aged: how to assess it?].

In the elderly hypertensive patient several of the basic procedures during evaluation should be repeated or performed with particular care. Most importantly multiple pressure measurements should be taken repeatedly, orthostatic reactions have to be sought by taking the blood pressure in the standing and lying patient and the carotid vessels have to be auscultated. If a carotid occlusion or stenosis is suspected, a Doppler ultrasound study is indicated prior to therapy. Generalized arteriosclerosis is probably rarely the cause of so called pseudohypertension. It should be considered when strikingly high blood pressure values contrast with clinical signs of low blood pressure. Finally if hypertension develops rapidly in an elderly patient renal arterial stenosis should be suspected.

Aged↗