PubMed Health⌕ Search

Biomedical subjects

A D Ho

Publications and source records attributed to A D Ho.

At least 19 recordsLinked to original sources
PubMed2006

Retroviral vector insertions in T-lymphocytes used for suicide gene therapy occur in gene groups with specific molecular functions.

Graft-versus-host disease (GvHD) is a severe complication in the context of allogeneic stem cell transplantation and adoptive immunotherapy. The transfer of a suicide gene into donor T-lymphocytes (TLCs) allows selective elimination of GvHD-causing cells. As retroviral gene transfer into hematopoietic stem cells can induce leukaemia, there is an urgent need also to analyze retroviral integration sites in TLCs. We examined suicide gene-transduced TLCs in four grafts and from four transplanted patients. One-hundred and fifteen integration sites were detected in vitro. Of these 90 could be mapped to the human genome; 50% (45) were located in genes and 32% (29) were detected 10 kb upstream or downstream of transcription start sites. We found a significant overrepresentation of genes encoding for proteins with receptor activity, signal transducer activity, transcription regulator activity, nucleic acid binding activity and translation regulator activity. Similar data were obtained from patient samples. Our results point to preferred vector integration patterns, which are specific for the target cell population and probably independent of selection processes. Thus, future preclinical analysis of the integration repertoire with abundant amounts of transduced cells could allow a prediction also for the in vivo situation, where target cells are scarce.

Animals↗
PubMed2006

Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial.

Piperacillin/tazobactam was compared with ceftazidime for the empirical treatment of febrile neutropenia in patients with acute leukemia or following autologous peripheral blood stem cell transplantation. Owing to inclusion criteria, it was possible for the same patient to be randomized several times. A total of 219 individual patients were admitted to a prospective randomized clinical study: 24 patients were included twice. Patients (23.5%) remained afebrile. Patients who developed febrile neutropenia were randomized to receive intravenous ceftazidime (n = 74 patients, group I) or piperacillin/tazobactam (n = 87 patients, group II). Response to first-line antibiotic treatment was seen in 55% (group I) and 53% (group II). After the addition of vancomycin, a further 19% (group I) and 24% (group II) of the patients became afebrile. Causes of fever were: microbiologically documented infection in 36 and 34 patients of group I and II; Clostridium difficile in eight and 12 patients of group I and II, and fever of unknown origin in 30 and 41 patients of group I and II. One patient died in each group. Single-agent therapy with piperacillin/tazobactam is as effective as ceftazidime in the treatment of neutropenic fever and is well tolerated. Direct and indirect costs of both treatment regimes are equivalent.

Acute Disease↗
PubMed2006

The initial phase of graft-versus-host disease is associated with a decrease of CD4+CD25+ regulatory T cells in the peripheral blood of patients after allogeneic stem cell transplantation.

The mechanisms that induce and control the alloimmune inflammation of graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (allo-SCT) are still incompletely understood. In the murine system, GvHD can be suppressed by CD4(+)CD25(+) regulatory T cells (TREG), which are generally involved in the suppression of inflammatory reactions. A disruption of the homeostasis between TREG and conventional T cells might therefore be associated with the inflammatory reactions of GvHD. We repetitively measured the frequency of TREG in the peripheral blood of 29 patients within the first 71-373 days after allo-SCT and correlated the results with the clinical course. We demonstrate that the initial phase of GvHD is associated with a significant reduction of TREG in the peripheral blood, while at later stages and during intensified immunosuppressive therapy, increased numbers of TREG appear. These results might indicate a pathogenic role for reduced numbers of TREG in the induction of human GvHD.

Adult↗
PubMed2006

Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization.

Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase and belongs to the Silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs), which play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We have isolated and characterized the human SIRT5 genomic sequence, which spans a region of 28,182 bp and which has one single genomic locus. Human SIRT5 consists of eight exons and is found in two isoforms, which encode a 310 aa and a 299 aa protein, respectively. Human SIRT5 is most predominantly expressed in heart muscle cells and in lymphoblasts. Fluorescence in situ hybridization analysis localized the human SIRT5 gene to chromosome 6p23.

Amino Acid Sequence↗
PubMed2005

Autologous haematopoietic stem cell transplantation for Behcet's disease with pulmonary involvement: analysis after 5 years of follow up.

BACKGROUND: Myeloablative chemotherapy and autologous haematopoietic stem cell transplantation (HSCT) may provide a therapeutic option in severe Behçet's disease (BD) with pulmonary involvement. CASE REPORTS: Two patients with BD with pulmonary involvement refractory to conventional immunosuppressive treatment underwent HSCT 1999. Stem cells were mobilised with cyclophosphamide (2 and 4 g/m(2)) and subsequently enriched ex vivo for CD34+ cells. The conditioning regimen used was melphalan (200 mg/m(2)). Outcome was measured by improvement of clinical features, function of affected organs, serological markers, need for immunosuppressive chemotherapy after transplant, and relapse. In both cases HSCT was successful, with good response and without serious complications. After 5 years of follow up one patient is in complete remission without immunosuppressive drugs and one has partial remission, needing low dose corticosteroids (8 mg/day). CONCLUSION: In these two patients myeloablative chemotherapy, followed by HSCT could be performed safely with marked improvement. In comparison with other observational studies the duration of more than 5 years of remission is remarkable, and its full duration is still unknown.

Adult↗
PubMed2005

[Integrated skills laboratory concept for undergraduate training in internal medicine].

BACKGROUND AND OBJECTIVE: An amendment to the German medical curriculum in April 2002 will place basic practical skills at the centre of medical training. We report here on the implementation and evaluation of an obligatory, tutor-guided, and integrated skills laboratory concept in the field of internal medicine. METHODS: To test the effectiveness of a skills laboratory training on OSCE performance a pilot study was carried out. The experimental group, of 77 students, participated in seven sessions of communication training, skills laboratory training, and bedside teaching, each lasting one and a half hours. The control group of 66 students had as many sessions but was only offered bedside-teaching. The evaluation of acceptance of skills' training as well as the related increase in individual competence is on-going (summer term 2004: n = 176 students). RESULTS: The integrated skills laboratory concept was rated at 3.5 (SD = 1.2) on a 5-point scale and was acknowledged as practice-oriented (M = 4.2; SD = 1.0) and relevant for doctors' everyday lives (M = 3.6; SD = 1.1). Increased levels of competence according to individual self-evaluations proved to be highly significant (p<.001), and results of the pilot study showed that the experimental group had a significantly better OSCE performance than the control group (p<.001). CONCLUSION: This pilot study shows that curriculum changes promoting basic clinical skills are effective and lead to an improved practical education of tomorrow's physicians. The integrated skills laboratory concept is well accepted and leads to a relevant increase in competence in the practice of internal medical. The presented skills laboratory concept in internal medicine is proving to be a viable and efficient learning tool.

Adult↗
PubMed2005

Molecular monitoring of tumour load kinetics predicts disease progression after non-myeloablative allogeneic stem cell transplantation in multiple myeloma.

BACKGROUND: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting. PATIENTS AND METHODS: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested. RESULTS: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P <0.001). The detection limit amounted to 1/10(4)-1/10(5) cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse. CONCLUSION: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention.

Adult↗
PubMed2005

Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma.

Conventional treatment or autologous transplantation has not been able to achieve long-term remission in patients with multiple myeloma (MM). Nonmyeloablative allogeneic transplantation might offer an option for cure without the high mortality associated with conventional conditioning. Here we present a retrospective analysis of patients with high-risk MM treated with nonmyeloablative allogeneic transplantation. In all, 52 patients with relapsed MM or high-risk features at diagnosis received 2 Gy TBI alone (n=3) or with fludarabine (n=49) as conditioning. Patients were heavily pretreated with a median of eight cycles of conventional chemotherapy and one or more autologous transplants for all but one patient. Regimen-related toxicity was low. Acute graft-versus-host disease II-IV occurred in 37% of patients, and 70% experienced chronic graft-versus-host disease (cGvHD). Median follow-up was 567 days, and transplant-related mortality was 17% in total. Estimated progression-free and overall survival at 18 months was 29.4 and 41.1%, respectively. Patients with cGvHD had a significantly higher progression-free survival, as did patients with up to eight cycles of pretreatment chemotherapy vs those with nine or more. In this highly pretreated patient group, disease control was unsatisfactory and our results suggest that a potential strategy might be to perform allogeneic transplant earlier in the course of the disease.

Adult↗
PubMed2005

New developments in stem cell biology and therapy. First meeting report from the working group of the German Society for Hematology and Oncology.

The call for the meeting which took place in Heidelberg 13 January 2005, resulted in a high number of contributions covering a diversity of topics: embryonal stem cell research; molecular signaling pathways; assay systems for primitive, mesenchymal and epithelial stem cells; markers for transdifferentiation; and theoretical considerations including biomathematical modeling of stem cell development. The program was rounded off by pre-clinical and clinical applications of stem cell therapies, including new mobilization agents, treatment of myocardial infarction and chemoprotective gene transfer to stem cells.

Epithelial Cells↗
PubMed2005

Thrombotic microangiopathy after combined autografting-allografting for multiple myeloma - report of three cases.

Thrombotic microangiopathy (TMA) has been described as a complication of bone marrow or stem cell transplantation. It is usually associated with high dose therapy for autologous transplantation or myeloablative conditioning in the allogeneic setting. Here we report three cases of TMA after reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation. All three patients had high dose Melphalan therapy with autologous stem cell support preceding the allogeneic transplantation for several weeks, which may have contributed to endothelial damage and subsequent development of TMA.

Antineoplastic Agents↗
PubMed2005

Myeloablative conditioning in myelofibrosis using i.v. treosulfan and autologous peripheral blood progenitor cell transplantation with high doses of CD34+ cells results in hematologic responses - follow-up of three patients.

Autologous transplantation after myeloablation for myelofibrosis with myeloid metaplasia provides a palliative therapy with a long term relief of symptoms. We have transplanted three patients with more than 5 x 10(6) CD34+ cells/kg body weight after myeloablation with treosulfan (total dose 42 g/m(2)) with a 18 months follow-up. Two of the patients had symptomatic splenomegaly and severe anemia. One patient had symptomatic splenomegaly and thrombocytopenia (< 100x10(9)/L). Granulocyte colony-stimulating factor-supported peripheral blood progenitor cell mobilization and collection was not associated with increased toxicity. Following transplantation we observed a prolonged reconstitution period of 28-38 days without fever or severe mucositis. All patients became free of erythrocyte transfusions or recovered to normal thrombocyte counts. There was a significant reduction of max. spleen size in one patient. We conclude that myeloablation with treosulfan and autologous PBPCT in these three patients with myelofibrosis was safe and useful.

Antigens, CD34↗
PubMed2004

Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX.

OBJECTIVE: To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. METHODS: The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). RESULTS: In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 +/- 12.9% s.d. vs 11.6 +/- 7.3% s.d.; P = 0.005). CONCLUSION: The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach.

Animals↗
PubMed2004

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for bone and soft-tissue sarcomas.

The role of high-dose chemotherapy (HDCT) with PBSCT in the treatment of bone and soft-tissue sarcomas is not established. In total, 27 patients (15 female, median age at TPL 30.6 years (range: 13-59)) were analyzed (Ewing sarcoma family n=8, osteosarcoma n=6, MPNST (malignant peripheral nerve sheath tumor) n=4, synovial sarcoma n=3, liposarcoma n=2, leiomyosarcoma n=2, rhabdomyosarcoma n=1, meningosarcoma n=1). Following chemotherapy and surgery complete remission (CR) (n=9), partial remission (PR) (n=10), stable disease (SD) (n=2) and progressive disease (PD) (n=6) were reached prior HDCT. Different HDCT conditioning regimens were used. One patient died due to cardiac arrest after HDCT. Except hematologic side effects, no WHO grade III-IV complications were observed. Four patients died within 6 months due to PD, disease recurred in another seven patients and led to death, 15 patients are alive with/without disease. The median progression-free survival (PFS) is 12.0 months (range: 0-58), in nine CR patients median PFS is 25.8 months (range: 3-58). Although the role of HDCT in the treatment of sarcomas is not defined, a subgroup of patients who achieved CR before HDCT could benefit from this therapy.

Adolescent↗