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Biomedical subjects

A Gruber

Publications and source records attributed to A Gruber.

At least 19 recordsLinked to original sources
PubMed2003

Generation of dendritic cells from lentiviral vector-transduced CD34+ cells from HIV+ donors.

Dendritic cells hold promise as adjuvant for immunotherapy for cancer and infectious diseases. We demonstrate that a significant number of cryopreserved peripheral blood CD34(+) cells from HIV-infected subjects can be transduced with a replication-incompetent lentiviral vector expressing HIV antigens. In addition, untransduced and transduced CD34(+) cells from HIV-infected individuals were able to differentiate into dendritic cells with strong T-cell stimulatory capacity. Thus, cryopreserved CD34(+) cells from HIV-infected subjects may prove useful for immunotherapy for HIV/AIDS.

Antigens, CD34↗
PubMed2003

[Diplopia after encircling procedure for retinal detachment].

PURPOSE: Our aim was to evaluate the frequency, duration and therapy of diplopia in primary position caused by motility disorders after retinal detachments treated only with encircling bands. METHODS: A retrospective review is made of 264 consecutive patients. RESULTS: At 6 months after surgery,18 (7%) out of the 264 patients had motility disorders with diplopia in primary position. In 55%, we found an esotropia and vertical deviation. For the treatment of diplopia, eight patients had prisms foils, five of whom are scheduled for surgery, six patients wear prism glasses and three patients did not return for follow up after their sight had been corrected with prisms. An operation for strabism was necessary in three cases, mainly because of hypertrophic scarring (adhesion syndrome), rather than suturing material or muscular decompensation. One patient needed eye occlusion for untreatable diplopia. The average change of refraction after the encircling procedure was -2.0 D. CONCLUSIONS: We recommend avoiding unnecessary preparation of the muscles when placing the encircling band (without destruction of the Tenon or periorbital tissue), motility exercises after the operation and full refractive correction for sensory compensation of deviations as early as possible. In addition, antiphlogistic drugs should be used to avoid scarring and treatment with prism lenses. Removal of the encircling band does not seem to improve the motility as the disorder is mainly caused by hypertrophic scarring, neither does mitomycin C or the application of viscoelastic substances.

Chronic Disease↗
PubMed2003

KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma.

The clinical and histopathological distinction between benign and malignant pheochromocytomas and paragangliomas is difficult, and reliable diagnostic markers are lacking. Here we have evaluated the prognostic value of human telomerase reverse transcriptase (hTERT) gene expression detected by reverse transcription PCR (RT-PCR); telomerase activity (TA) measured by TRAP (telomeric repeat amplification protocol) assay; immunohistochemical staining for Ki-67/MIB-1; and the mRNA expression of matrix metalloproteinase (MMP)-2 and EMMPRIN (extracellular matrix metalloproteinase inducer) analyzed by in situ hybridization in 32 primary pheochromocytomas or abdominal paragangliomas. hTERT was expressed in 7/11 malignant tumors (defined as presence of metastasis and/or extensive local invasion) as compared with in 2/21 benign tumors. All of the benign tumors showed <1% proliferative activity, as measured by Ki-67/MIB-1 staining. In all three patients with malignant tumors who developed metastases and/or invasive local recurrence during follow-up, the tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. TA was not a significant discriminator between benign and malignant tumors, and the value of EMMPRIN and MMP-2 as predictive markers was limited. In conclusion, the findings imply that the combined use of Ki-67/MIB-1 and hTERT, in addition to histopathology, provides a highly specific tool to identify benign pheochromocytoma and abdominal paraganglioma cases that are not at risk of developing recurrent or metastatic disease.

Abdominal Neoplasms↗
PubMed2003

[Bronchopneumonia and polyarthritis due to Mycoplasma bovis in a calf].

This case report describes gross lesions and histopathological findings in a 3-months-old calf originating from a feedlot with approximately 400 cattle. In this animal and additional 14 cattle of similar age, which were kept together in the same stable, swollen joints had occurred suddenly. The examination of this calf showed that a severe polyarthritis induced by haematogenous spread of Mycoplasma bovis following bronchopenumonia was present, which was characterised by necrotising lesions of the joint capsules and severe cartilage erosions.

Animals↗
PubMed2002

A survey of the inter- and intraspecific RAPD markers of Eimeria spp. of the domestic fowl and the development of reliable diagnostic tools.

Coccidiosis of domestic fowl is a protozoan disease, caused by seven distinct species of the genus Eimeria, which is responsible for important economic losses in poultry production. In order to select RAPD primers for the discrimination of these seven Eimeria species, we carried out an initial screening using samples of E. acervulina, E. tenella and E. maxima. Out of 150 primers tested, 110 generated band profiles specific for each one of these species. A subset of 14 oligonucleotides were also tested for the simultaneous differentiation of the seven species, resulting in 11 discriminative primers. The intraspecific discrimination was assessed for five different species, using samples from different geographic regions including three continents. Numerous primers exhibited highly discriminative band profiles containing strain-specific markers, with a higher variability being observed among strains of E. acervulina than among E. tenella and E. maximastrains. However, no major differences were observed in the band patterns from strains collected in locations near to one another compared to strains originating from distantly located regions. Because RAPD is a technique performed under low stringency conditions, it suffers from poor reproducibility. Aiming at obtaining more reliable markers that might be universally used, we started an effort to convert species-specific RAPD fragments into SCAR markers. An initial conversion of 25 RAPD markers into SCARs, followed by validation of their specificity, resulted in 14 totally new Eimeria species-specific markers that can be used for the molecular diagnosis of the seven species that infect domestic fowl. This work represents a first step in the development of a set of species-specific SCARs that will be useful as tools for molecular diagnosis, genome mapping, and genetic diversity studies.

Animals↗
PubMed2002

Comparison of the genomes of two Xanthomonas pathogens with differing host specificities.

The genus Xanthomonas is a diverse and economically important group of bacterial phytopathogens, belonging to the gamma-subdivision of the Proteobacteria. Xanthomonas axonopodis pv. citri (Xac) causes citrus canker, which affects most commercial citrus cultivars, resulting in significant losses worldwide. Symptoms include canker lesions, leading to abscission of fruit and leaves and general tree decline. Xanthomonas campestris pv. campestris (Xcc) causes black rot, which affects crucifers such as Brassica and Arabidopsis. Symptoms include marginal leaf chlorosis and darkening of vascular tissue, accompanied by extensive wilting and necrosis. Xanthomonas campestris pv. campestris is grown commercially to produce the exopolysaccharide xanthan gum, which is used as a viscosifying and stabilizing agent in many industries. Here we report and compare the complete genome sequences of Xac and Xcc. Their distinct disease phenotypes and host ranges belie a high degree of similarity at the genomic level. More than 80% of genes are shared, and gene order is conserved along most of their respective chromosomes. We identified several groups of strain-specific genes, and on the basis of these groups we propose mechanisms that may explain the differing host specificities and pathogenic processes.

Gene Order↗
PubMed2002

Long-term follow-up of patients >or=60 yr old with acute myeloid leukaemia treated with intensive chemotherapy.

It is still controversial how to treat elderly patients with acute myeloid leukaemia (AML), and results have been poor with most regimens. We report the long-term results of a randomised study performed by the Leukaemia Group of Middle Sweden during 1984-88 comparing two intensive chemotherapeutic drug combinations. Ninety patients >or=60-yr old with untreated AML were randomly allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and thioguanine (TAD) (43 patients) or a combination in which aclarubicin was substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%) entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in the TAA group (ns). The CR rate in patients 70 yr 14/48 (29%) (P<0.0001). Early death within 30 d after treatment initiation was more often seen in patients >70 yr than in patients or=10 yr after inclusion of the last patient, 5/90 patients (one in the TAD group and four in the TAA group, respectively) were still alive, four in continuous complete remission and one in second complete remission. Thus, both treatment regimens appear to have similar efficacy, with a relatively high complete remission rate, and a reasonable survival as compared to other studies including some long-term survivors. However, early deaths are still numerous, particularly in patients above 70 yr of age, and the relapse rate is substantial.

Aclarubicin↗
PubMed2002

Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma.

Meningiomas comprise a wide range of morphological patterns. We describe unusual fibrous meningeal tumours in two patients, composed of extensive non-calcifying collagenous whorls of varying size, resembling non-calcified psammoma bodies, while interposed tumour cells are sparse. Immunohistochemistry showed expression of S-100, vimentin and glial fibrillary acidic protein, whereas only single tumour cells stained for epithelial membrane antigen. Electron microscopy detected desmosomes or desmosome-like structures in both specimens. We conclude that these tumours represent a peculiar whorling-sclerosing variant of fibrous meningioma. Recognition of this meningioma variant is important in the differential diagnosis of meningioma versus other fibrous tumours of the meninges, including solitary fibrous tumours of the meninges, unusual forms of desmoplastic gliomas or chondroid tumours.

Aged↗
PubMed2001

Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-specific CTLs.

Dendritic cells (DCs) can acquire antigen(s) from apoptotic tumor cells, resulting in an immunogen that can induce class I-restricted cytotoxic T lymphocytes (CTLs) and protective tumor rejection. Here, we investigated whether DCs derived from ascitic monocytes of patients with ovarian carcinoma could kill autologous ovarian tumor cells and if as a result they would acquire antigen(s) enabling them to induce a tumor-specific immunity. We found that the immature DCs could exert a significant cytotoxicity towards autologous and allogeneic ovarian tumor cells. This cytotoxicity was independent of Ca(2+) and could be inhibited by anti-Fas IgG1 monoclonal antibody, indicating the involvement of the Fas/Fas ligand (FasL) pathway in the cytotoxic mechanism. Further supporting this conclusion, the ascitic monocyte-derived DCs expressed high levels of FasL mRNA and intracellular FasL and significant levels of Fas were also revealed on the surface of ovarian tumor cells. Coculture of DCs induced apoptosis in ovarian carcinoma cells, as well as uptake of apoptotic tumor cells into the cytoplasma of the DCs, as visualized by immunofluoresence. Autologous DCs cocultured with apoptotic ovarian tumor cells were able to specifically stimulate tumor-specific CTLs, whereas DCs cocultured with necrotic ovarian cells were unable to do so. Collectively, these results demonstrate that immature DCs can kill autologous ovarian carcinoma cells via the Ca(2+)-independent Fas/FasL pathway and that this may have important consequences for their ability to stimulate tumor-specific CTLs.

Antibodies, Monoclonal↗
PubMed2001

Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function.

Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS.

Cell Division↗
PubMed2001

The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Expressed Sequence Tags↗
PubMed2001

Cholesterol catabolism in patients with acute myelogenous leukemia and hypocholesterolemia: suppressed levels of a circulating marker for bile acid synthesis.

Hypocholesterolemia is a frequent finding in patients with acute myelogenous leukemia (AML) and in other types of malignancies. Since bile acids are major excretion products of cholesterol, the hepatic degradation of cholesterol to bile acids was investigated in AML patients by analyzing a circulating marker for bile acid synthesis. In addition, plasma levels of a marker for cholesterol synthesis were determined. The plasma levels of 7alpha-hydroxy-4-cholesten-3-one, reflecting bile acid production, were markedly lower in patients with AML than in healthy controls. The median levels were 3.3 and 18.5ng/ml (P<0.0001) in the AML patients (n=29) and the healthy subjects (n=16), respectively. The plasma levels of 7-dehydrocholesterol, reflecting hepatic cholesterol synthesis, were similar for the AML patients and the controls. The results show that the conversion of cholesterol to bile acids was suppressed in AML patients, a phenomenon that may result in a decreased intestinal absorption of cholesterol and subsequent hypocholesterolemia.

Aged↗
PubMed2001

Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells.

Recent evidence suggests that the Myc and Mad1 proteins are implicated in the regulation of the gene encoding the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. We have analyzed the in vivo interaction between endogenous c-Myc and Mad1 proteins and the hTERT promoter in HL60 cells with the use of the chromatin immunoprecipitation assay. The E-boxes at the hTERT proximal promoter were occupied in vivo by c-Myc in exponentially proliferating HL60 cells but not in cells induced to differentiate by DMSO. In contrast, Mad1 protein was induced and bound to the hTERT promoter in differentiated HL60 cells. Concomitantly, the acetylation of the histones at the promoter was significantly reduced. These data suggest that the reciprocal E-box occupancy by c-Myc and Mad1 is responsible for activation and repression of the hTERT gene in proliferating and differentiated HL60 cells, respectively. Furthermore, the histone deacetylase inhibitor trichostatin A inhibited deacetylation of histones at the hTERT promoter and attenuated the repression of hTERT transcription during HL60 cell differentiation. In addition, trichostatin A treatment activated hTERT transcription in resting human lymphocytes and fibroblasts. Taken together, these results indicate that acetylation/deacetylation of histones is operative in the regulation of hTERT expression.

Acetylation↗
PubMed2001

Telomerase activity in plasma cell dyscrasias.

Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM.

Adult↗
PubMed2001

Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma--case report and review of the literature.

The authors present an unusual complication of a recurrent chiasmal/hypothalamic pilocytic astrocytoma. From his second year of life onwards, the patient was repeatedly operated on and also underwent external radiation therapy (54 Gy total dose) 1 month after the first subtotal tumor resection. Nine years after irradiation, the patient was referred to our center with a sudden onset of severe headache, vomiting and neck stiffness. Computed tomography, magnetic resonance imaging, and cerebral angiography demonstrated an intratumoral, intraventricular, and subarachnoidal hemorrhage from an anterior communicating artery aneurysm encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient recovered nicely from the hemorrhage. Three years later, the patient suddenly died of cardiac failure. Autopsy disclosed vessel wall changes compatible with radiation-induced vasculopathy. In light of this finding, the importance of radiation therapy and intracranial neoplasms for aneurysm formation is discussed.

Acute Disease↗
PubMed2001

In vitro topo II--DNA complex accumulation and cytotoxicity of etoposide in leukaemic cells from patients with acute myelogenous and chronic lymphocytic leukaemia.

Topoisomerase II (topo II) is the target enzyme of etoposide, and DNA--topo II complex accumulation is considered crucial for the cytotoxic effect. We used a SDS--KCl precipitation assay to determine the complex accumulation induced by etoposide in leukaemic cells isolated from 58 patients, 31 with acute myelogenous leukaemia (AML), and 27 with chronic lymphocytic leukaemia (CLL). To investigate whether the sensitivity towards etoposide was dependent on the complex accumulation in the cells, we investigated the drug-induced DNA damage using a DNA unwinding assay and the in vitro cytotoxicity of etoposide using the MTT assay. AML cells had higher complex accumulation (P=0.006) and more DNA damage (P=0.029) compared with CLL cells. The data support a relationship between etoposide-induced complex accumulation and DNA damage in leukaemic cells from AML and CLL patients. However, the induced DNA damage did not translate to in vitro cytotoxicity, suggesting that other factors, such as DNA repair and apoptosis functions, also play important roles to determine the etoposide sensitivity.

Adult↗