Search PubMed⌕ Search

Biomedical subjects

R Haas

Publications and source records attributed to R Haas.

At least 91 records · Page 5Linked to original sources
PubMed2000

Intercellular adhesion molecular 1 on monocytes mediates adhesion as well as trans-endothelial migration and can be downregulated using antisense oligonucleotides.

The intercellular adhesion molecule 1 (ICAM-1) on endothelial cells is involved in the recruitment of leukocytes to inflammatory sites. In contrast to ICAM-1 expression on endothelial cells, little is known about its function in leukocytes in inflammation. Using ICAM-1-directed anti-sense oligodeoxyribonucleotides (ODNs), we examined the role of ICAM-1 expression on monocytes and lymphocytes for adhesion and trans-endothelial migration. As determined by flow cytometry, a downregulation of the ICAM-1 expression of 50% was observed on peripheral blood mononuclear cells (PBMCs) after their transfection with anti-sense ODNs using cationic lipids. The decrease in the level of ICAM-1 expression in PBMCs was associated with a 36% inhibition of adhesion to interleukin-1beta-stimulated endothelial cells and a 40% reduction of trans-endothelial migration. Gating on particular subsets of the PBMC, the downregulation of ICAM-1 and the functional effects could be ascribed to monocytes, while no significant inhibition was found for lymphocytes. This could be explained by differences in cellular ODN uptake. Since the ligands of ICAM-1 are not expressed on endothelial cells, the results suggest a homotypic interaction among monocytes. In conclusion, in addition to ICAM-1 expression on endothelial cells, ICAM-1 expression on monocytes mediates adhesion and transendothelial migration. This might be relevant for the clinical use of ICAM-1-directed anti-sense ODNs for the treatment of inflammatory diseases, because monocytes appear to be suitable target cells in which to achieve anti-inflammatory effects.

Cell Adhesion↗
PubMed2000

High-dose therapy with peripheral blood stem cell transplantation for patients with relapsed or refractory Hodgkin's disease: long-term outcome and prognostic factors.

From March 1986 to March 1998, 82 patients with relapsed or refractory Hodgkin's disease underwent high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) transplantation in our center. This is a retrospective analysis of the long-term clinical outcome. There were 52 males and 30 females with a median age of 32 years (range 18-59 years). Prior to transplantation, 36 patients were in complete remission (CR), 34 in partial remission (PR), and 12 had refractory disease after salvage therapy. For HDCT, 78 patients were treated with CBV (cyclophosphamide, 6.0-6.8 g/ m2; etoposide, 1.0-1.6 g/m2; carmustine, 0.45-0.8 g/m2), while four patients received different regimens. Probability of freedom from progression (FFP), overall survival (OS), and event-free survival (EFS) at 5 years of the entire group was 63%, 61%, and 54%, respectively. Early mortality rate ( < or = 100 days) declined from 17% to 6% after 1992. Five patients died of late transplant-related complications (> 100 days), including secondary lymphoma and leukemia in two patients. None of the refractory patients survived beyond 3.5 years. Multivariate analyses identified extranodal sites of disease at relapse and refractory disease status prior to transplantation as significant prognostic factors for FFP, EFS, and OS. As we have shown in our study, remarkable progress was achieved in reducing early morbidity and mortality over time, but this was associated with only a slight, not significant improvement of long-term outcome (OS 66% vs 57% at 5 years for patients undergoing PBSC transplantation before and after 1992, P = 0.26). Although the results as a whole are encouraging for chemosensitive patients, new therapeutic strategies are needed to reduce toxicity and improve the clinical outcome of patients, especially of those with a less favorable prognosis.

Adolescent↗
PubMed2000

Detection of tumor cells in leukapheresis products from patients with breast cancer using immunocytochemical staining method.

We used a combination of 4 monoclonal antibodies (BM7, BM8 against MUC1, 5D3 against CK8,18,19 and HEA125 against human epithelial antigen) and a sensitive immunocytochemical staining using cytospin preparation to identify breast tumor cells in leukapheresis products (LP). This assay allowed detection of one tumor cell in 1x10(6) mononuclear cells (MC). In clinical specimens, tumor cells were detected in LP from 6 of 42 (14.3%) patients in the adjuvant treatment group, from 2 of 11 (18.2%) patients in the neoadjuvant treatment group and from 9 of 43 (20.1%) in the group of patients with metastatic disease. Tumor cell counts ranged from 0.25-5 cells in 1x10(6) normal cells per LP. The median tumor cell concentration was higher in specimens from patients with metastatic disease (median=0.96) than in specimens from patients in the adjuvant and neoadjuvant treatment groups (median=0.5 and 0.75). No significant differences between the epithelial cell positive group and the epithelial cell negative group with respect to tumor size, lymph nodes involvement, tumor grade, histological type and receptor were found. We conclude that immunocytochemical staining of cytospin preparation is a sensitive and simple method to detect and quantitate breast cancer cells in LP.

Adult↗
PubMed2000

Efficacy of continuous infusion of ceftazidime for patients with neutropenic fever after high-dose chemotherapy and peripheral blood stem cell transplantation.

Neutropenia is an important complication of high-dose chemotherapy (HDCT). Neutropenic patients presenting with fever are routinely hospitalized for treatment with broad-spectrum antibiotics. Neutropenia up to 10 days is associated with a low-risk profile, and antimicrobial therapy administered on an outpatient basis might be an alternative to admission to hospital. This prospective study evaluates the safety of a continuous infusion of ceftazidime in neutropenic patients after HDCT and peripheral blood stem cell transplantation (PBSCT). From September 1995 to October 1999, 81 patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion per 24 h of ceftazidime using a portable infusion pump. If the fever persisted for 72 h, a glycopeptide antibiotic was added. The median patients' age was 44 years. Fifty-two of 81 patients (64%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, a further 17 patients (21%) became afebrile. The causes of fever were septicaemia in 11 patients, pneumonia in two and fever of unknown origin in 68 patients. Fifty-eight episodes (72%) were successfully managed by outpatient treatment alone. The reason for admission to hospital was the change to imipenem/cilastin, which had to be administered three times per day (12 patients), severe mucositis with parenteral nutrition (eight patients), or a Karnovsky index </=60 (three patients). In six of these cases, outpatient treatment was resumed after a brief period of in-patient care. In no case was the treatment terminated because of failure of the pump. With daily follow-up and close monitoring for development of complications, it is possible to discharge patients earlier after HDCT and PBSCT, thereby decreasing costs.

Adolescent↗
PubMed2000

Biostimulation of bone marrow cells with a diode soft laser.

In recent years, the use of low-intensity red light in regeneration of soft tissue has been increasingly pursued. As far as hard tissue is concerned, the biostimulating effect of laser has already been demonstrated successfully in more rapid healing of tibial bone fractures in mice at a dosage of 2.4 J. However, the effect of light of a low dose laser directly on osteoblasts has not been investigated yet. The aim of this study was to determine the effect of continuous wave diode laser irradiation on osteoblasts derived mesenchymal cells. Three groups of 10 cultures each were irradiated 3 times (days 3, 5, 7) with a pulsed diode soft laser with a wavelength of 690 nm for 60 s. Another 3 groups of 10 cultures each were used as control groups. A newly developed method employing the fluorescent antibiotic tetracycline was used to compare bone growth on these culture substrates after a period of 8, 12 and 16 days, respectively. It was found that all lased cultures demonstrated significantly more fluorescent bone deposits than the non-lased cultures. The difference was significant, as tested by the Tukey Test (P < 0.0001) in the cultures examined after 16 days. Hence it is concluded that irradiation with a pulsed diode soft laser has a biostimulating effect on osteoblasts in vitro, which might be used in osseointegration of dental implants.

Animals↗
PubMed2000

Alternative to the median region of the palate for placement of an orthodontic implant.

Tooth-borne anchorage may be one of the greatest limitations of modern orthodontic treatment, because teeth move in response to forces. Previous investigators have placed temporary implants in the median-sagittal palate in order to establish maximum anchorage. This area, however, may be characterized by relatively low vertical bone support. The aim of this study was therefore to find an alternative palatal implant site which offers a higher amount of bone support. This study comprised 22 patients wishing for maximum anchorage underwent presurgical diagnostic evaluation by means of low-dose dental CT. The measuring results regarding vertical bone volume and the position of the neighbouring tooth roots were used as the basis for further treatment. The statistical data analysis indicated an area suitable for implant placement in the group of patients examined. This area was located 6 to 9 mm posterior to the incisive foramen and 3 to 6 mm paramedian, under avoidance of the mid-palatal suture. The patients showed such a great range of variation in vertical bone volume that a preoperative diagnostic evaluation also seems to be recommendable when very short implants are used in order to avoid perforations of the lower nasal duct.

Adolescent↗
PubMed2000

Prognostic factors for the clinical outcome of patients with follicular lymphoma following high-dose therapy and peripheral blood stem cell transplantation (PBSCT).

This is a report on 111 patients with advanced stage follicular lymphoma who where autografted using PBSC. Seventy patients were enrolled in first remission, whereas 41 were treated in second or higher remission. High-dose therapy consisted of total body irradiation plus cyclophosphamide in 103 patients, while eight patients received BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan). Autografts contained 8.1 +/- 0.6 x 106 CD34+ cells/kg body weight. At a median follow-up of 44.2 months from PBSCT (range 4.9-77.4 months), 93 patients are alive, with a probability of overall and relapse-free survival (RFS) of 83% and 64%, respectively. A significantly higher probability of relapse was associated with male gender, involvement of more than eight lymph node areas, extra-nodal manifestations other than bone marrow and PBSCT performed in second or higher remission. In the latter group of patients, previous radiotherapy was associated with poor prognosis. The relevance of chemosensitivity as a prognostic factor was reflected by a better RFS in patients who had achieved complete remission at the time of PBSC mobilization. In a multivariate analysis, involvement of eight or more lymph nodes and high-dose therapy performed in second or higher remission were independent prognostic factors.

Adult↗
PubMed2000

Bone marrow-derived cells as carriers of recombinant immunomodulatory cytokine genes to lymphoid organs.

The purpose of this study was to determine the feasibility of cytokine gene delivery to lymphatic tissue using transduced bone marrow-derived cells. MBAE and pBABE retroviral vectors carrying the genes for murine interleukin-4 and the selection marker neomycin phosphotransferase (neo) were used to transduce bone marrow-derived dendritic cells (DC) and hematopoietic stem cells (HSC). A transduction efficiency of 11-33% for HSC and 2-10% for DC was achieved. Transduced HSC and DC released 55-170 pg of recombinant interleukin-4 per 1 x 10(6) cells/mL in vitro. To study the migration of the cells in vivo, we introduced the transduced cells into syngenic mice. DC were injected subcutaneously into the front limbs of unconditioned mice and HSC were intravenously administered to irradiated mice. The distribution of the transduced cells was studied by quantitative polymerase chain reaction for the neo gene as a marker. After 3 days, DC migrated to the axillary lymph nodes in the drainage area of the injection site and were detectable up to 5 days. After intravenous administration of transduced HSC, the neo gene could be found in up to 100 copies/5 x 10(3) cells in mesenterial lymph node, spleen, bone marrow, thymus, and liver. The distribution of the transduced cells was heterogenous: in different mice, different organs showed high copies of the neo gene after 10 and 13 days. After 39 days, two of three mice were negative for neo in all organs analyzed. In conclusion, bone marrow-derived cells can be genetically engineered ex vivo to deliver recombinant cytokine genes to lymphoid organs in vivo. In particular, DC might be candidate cells for use in immunomodulatory gene therapy for autoimmune diseases and cancer.

Animals↗
PubMed2000

The impact of autologous stem cell transplantation on the prognosis of mantle cell lymphoma: a joint analysis of two prospective studies with 46 patients.

INTRODUCTION: The purpose of this analysis was to investigate if early sequential high-dose therapy with autologous stem cell transplantation (ASCT) can improve the poor prognosis of patients with disseminated mantle cell lymphoma (MCL). PATIENTS AND METHODS: A joint analysis of two parallel single center studies was performed. Both were characterized by a sequential high-dose therapy consisting of an intensive chemotherapy ('HAM' or 'Dexa-BEAM') for mobilization of peripheral blood stem cells and induction of minimal disease followed by a total body irradiation-containing myeloablative regimen and ASCT. Forty-six patients with reference panel-confirmed stage III/IV MCL were included. Thirty-four patients were accrued to the protocol immediately after diagnosis ('upfront ASCT' group). These 34 patients received a standard first-line regimen prior to mobilization. The remaining 12 patients were put on the protocol later during the course of their disease ('delayed ASCT' group). RESULTS: All patients were in remission after mobilization chemotherapy and proceeded to ASCT; there were no exclusions due to poor response, poor mobilization, or patient refusal. With a follow-up of 24 (2-73) months post transplant, the event-free and overall survival probabilities at 2 years were 77 and 100% for the upfront ASCT group compared to 30% (P=0.0007) and 54% (P=0.0016) for the delayed ASCT group. Event-free and overall survival tended to be longer in the upfront ASCT group than in the delayed ASCT group also if calculated from initial diagnosis (76 and 93% vs 42 and 63%, respectively, at 4 years after diagnosis; median follow-up 35 months), although this was not statistically significant. Besides timing of ASCT, only spleen size was identified as an independent predictor of survival by univariate and multivariate analysis. CONCLUSION: ASCT is not curative but may improve the prognosis of patients with MCL if performed as part of an intensive first-line treatment strategy. In contrast, the benefits of this approach for salvaging individuals with relapsed disease appear to be limited.

Adult↗
PubMed2000

In vivo depletion of B cells using a combination of high-dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non-Hodgkin's lymphoma.

We performed a pilot study including rituximab (Mabthera; IDEC-C2B8, Hoffmann-La Roche) with a sequential high-dose therapy protocol in 15 patients with follicular and three patients with mantle cell lymphoma and studied the potential of the chemoimmunotherapy to induce depletion of malignant B cells in vivo. Our treatment protocol included induction with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, followed by peripheral blood stem cell (PBSC) mobilization using high-dose cytosine arabinoside (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3) (HAM), preceeded by rituximab (375 mg/m2). The proportion of CD19+ B cells in blood and bone marrow decreased from 1.2 +/- 0.4% to 0.13 +/- 0. 1% (P = 0.01) and from 2.7 +/- 0.8% to 0.8 +/- 0.5% (P = 0.03) respectively. The number of t(14;18)-positive cells in blood and bone marrow progressively decreased with treatment, as assessed by the quantitative real-time PCR assay in four patients. Conversion to PCR-negativity was achieved in the peripheral blood (PB) of seven informative patients. Leucaphereses were performed during the granulocyte colony-stimulating factor (G-CSF)-supported leucocyte recovery phase. In 17 of 18 patients, a median of 15.1 x 106 CD34+ cells/kg body weight (BW) could be harvested by a single procedure for enrichment by an immunomagnetic method. Leucapheresis products contained 51.3 +/- 28.8 x 104 CD19+ B cells/kg BW (mean) and were t(14;18) PCR negative in all seven informative patients. These data compare favourably with results obtained in patients treated with the same regimen without rituximab. The high-dose therapy (n = 12 patients), including total body irradiation (14.4 Gy) and cyclophosphamide (200 mg/kg BW), was also preceeded by rituximab. Recovery of neutrophils to > 0.5 x 109/l and of platelets to > 20 x 109/l required a median of 13.5 and 11.5 d (range 11-24 and 9-24 d) respectively. In conclusion, the addition of the CD20 antibody to chemotherapy ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of tumour cells and with conserved engraftment capability.

Adult↗
PubMed2000

Mobilization of CD34+ haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4.

The beta1 integrin very late antigen 4 (VLA-4) plays a central role in mobilization and homing of CD34+ cells. In this study, we examined the activation state of VLA-4 on CD34+ cells from bone marrow (BM) and peripheral blood (PB) by flow cytometry using a vascular cell adhesion molecule I-immunoglobulin (VCAM-I/IgG) fusion protein as soluble ligand. In an intraindividual analysis, we found a significantly reduced affinity and avidity of the VLA-4 receptor on CD34+ cells from PB during granulocyte colony-stimulating factor (G-CSF)-enhanced marrow recovery in comparison with steady-state BM. Moreover, the amount of circulating CD34+ cells during marrow recovery was inversely related to the activation state but not to the expression level of VLA-4, suggesting that a modulation of the functional state of VLA-4 is involved in the mobilization of CD34+ cells. Moreover, VLA-4 function on CD34+ cells from BM was associated with the maturation state of CD34+ cells as high-affinity VLA-4 receptors were observed on the vast majority of more primitive CD34+ cells. In addition, we found that Mg2+ ions as well as co-incubation of CD34+ cells with endothelial cells resulted in an activation of the VLA-4 receptor. In conclusion, modulation of the functional state of VLA-4 appears to be of relevance for the mobilization and homing of CD34+ haematopoietic stem cells.

Antigens, CD34↗
PubMed2000

Long-term remission after intensive chemotherapy in advanced myelodysplastic syndromes is generally associated with restoration of polyclonal haemopoiesis.

The clonality of peripheral blood cells was assessed in eight female patients with myelodysplastic syndrome (MDS) by means of the human androgen receptor gene-based assay (HUMARA). The patients were in complete remission for a median follow-up time of 83 months after intensive chemotherapy. X-chromosome inactivation patterns (XCIPs) indicated polyclonal haemopoiesis in five patients. Two patients had skewed lyonization (i.e. unbalanced XCIPs in both granulocytes and T cells) and one patient presented monoclonal granulocytes together with polyclonal T cells. We conclude that long-term remission in MDS following intensive chemotherapy is usually associated with polyclonal haemopoiesis.

Adult↗
PubMed2000

Prevalence of cutaneous manifestations in 200 patients with eating disorders.

BACKGROUND: Eating disorders are increasing and show a variety of symptoms. They mainly include anorexia nervosa (AN), bulimia nervosa (BN), and eating disorders not specified (EDNOS). They predominate in females and represent an important danger, especially in teenagers. In serious cases, they may be life-threatening. Objective To determine the prevalence of cutaneous findings in patients with eating disorders and to compare the results with those found in the literature. METHODS: An observational, transverse, and prospective study was performed. Two hundred patients of recent admission to ALUBA (association that fights against BN and AN), a psychiatric unit for eating disorders, were included: 122 BN; 62 AN; 16 EDNOS. RESULTS: Patients with eating disorders show dermatologic manifestations (alopecia, xerosis, hypertrichosis, caries, nail fragility) that are secondary to starvation. Russell's sign, seen as calluses on the dorsal aspect of the hands, is a consequence of self-induced vomiting and the local trauma of the superior incisors. This sign represents a compensatory behavior to overeating and predominates in the BN group. CONCLUSION: The recognition of dermatologic signs could be of immense value and could lead to the early diagnosis and treatment of these eating disorders.

Adolescent↗
PubMed2000

Genotoxic markers among butadiene polymer workers in China.

While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.

Adult↗
PubMed2000

Rapid and specific detection of Helicobacter pylori macrolide resistance in gastric tissue by fluorescent in situ hybridisation.

BACKGROUND: The development of macrolide resistance in Helicobacter pylori is considered an essential reason for failure of antibiotic eradication therapies. The predominant mechanism of resistance to macrolides, particularly clarithromycin, is based on three defined mutations within 23S rRNA, resulting in decreased binding of the antibiotic to the bacterial ribosome. AIM: To develop an rRNA based whole cell hybridisation method to detect Helicobacter species in situ within gastric tissue, simultaneously with its clarithromycin resistance genotype. METHODS: A set of fluorescent labelled oligonucleotide probes was developed, binding either to H pylori 16S rRNA or 23S rRNA sequences containing specific point mutations responsible for clarithromycin resistance. After hybridisation and stringent washing procedures, labelling of intact single bacteria was monitored by fluorescence microscopy. The new approach was compared with PCR based assays, histology, and microbiological culture. RESULTS: In comparison with the phenotypic resistance measurement by E test, the genotypic clarithromycin resistance correlated perfectly (100%) for 35 H pylori isolates analysed. In a set of gastric biopsy specimens (27) H pylori infection was confirmed by histology (17/27) and correctly detected by whole cell hybridisation. Five clarithromycin resistant strains were identified in gastric tissue specimens directly. Furthermore, non-cultivable coccoid forms of H pylori were easily detectable by whole cell hybridisation. CONCLUSIONS: Whole cell hybridisation of rRNA holds great promise for cultivation independent, reliable, and rapid (three hours) genotypic determination of clarithromycin resistance in H pylori. Compared with PCR techniques it is independent of nucleic acid preparations, not prone to inhibition, and allows semiquantitative visualisation of the bacteria within intact tissue samples.

Anti-Bacterial Agents↗
PubMed2000

The role of cytokines and adhesion molecules for mobilization of peripheral blood stem cells.

CD34(+) hematopoietic stem cells from peripheral blood are commonly used for autologous or allogeneic transplantation following high-dose therapy in malignant diseases. The introduction of hematopoietic growth factors such as G-CSF has greatly facilitated the mobilization of CD34(+) cells. The mechanism of stem cell mobilization is not yet clear. It seems to be a multistep process with a crosstalk between cytokines and adhesion molecules. In this review, the role of hematopoietic growth factors, chemokines, and adhesion molecules for mobilization and homing of CD34(+) cells is summarized. In addition, factors influencing the cytokine-induced mobilization in patients and healthy donors are described. The review closes with an overview of new classes of mobilizing drugs such as monoclonal antibodies, specific peptides, or antisense oligonucleotides targeting adhesion molecules.

Antigens, CD34↗