Biomedical subjects

H Huber

Publications and source records attributed to H Huber.

At least 19 recordsLinked to original sources

PubMed2006

PDGF essentially links TGF-beta signaling to nuclear beta-catenin accumulation in hepatocellular carcinoma progression.

The cooperation of Ras - extracellular signal-regulated kinase/mitogen-activated protein kinase and transforming growth factor (TGF)-beta signaling provokes an epithelial to mesenchymal transition (EMT) of differentiated p19(ARF) null hepatocytes, which is accompanied by a shift in malignancy and gain of metastatic properties. Upon EMT, TGF-beta induces the secretion and autocrine regulation of platelet-derived growth factor (PDGF) by upregulation of PDGF-A and both PDGF receptors. Here, we demonstrate by loss-of-function analyses that PDGF provides adhesive and migratory properties in vitro as well as proliferative stimuli during tumor formation. PDGF signaling resulted in the activation of phosphatidylinositol-3 kinase, and furthermore associated with nuclear beta-catenin accumulation upon EMT. Hepatocytes expressing constitutively active beta-catenin or its negative regulator Axin were employed to study the impact of nuclear beta-catenin. Unexpectedly, active beta-catenin failed to accelerate proliferation during tumor formation, but in contrast, correlated with growth arrest. Nuclear localization of beta-catenin was accompanied by strong expression of the Cdk inhibitor p16(INK4A) and the concomitant induction of the beta-catenin target genes cyclin D1 and c-myc. In addition, active beta-catenin revealed protection of malignant hepatocytes against anoikis, which provides a prerequisite for the dissemination of carcinoma. From these data, we conclude that TGF-beta acts tumor progressive by induction of PDGF signaling and subsequent activation of beta-catenin, which endows a subpopulation of neoplastic hepatocytes with features of cancer stem cells..

Anoikis↗

PubMed2006

A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes.

Polarized hepatocytes expressing hyperactive Ha-Ras adopt an invasive and metastatic phenotype in cooperation with transforming growth factor (TGF)-beta. This dramatic increase in malignancy is displayed by an epithelial to mesenchymal transition (EMT), which mimics the TGF-beta-mediated progression of human hepatocellular carcinomas. In culture, hepatocellular EMT occurs highly synchronously, facilitating the analysis of molecular events underlying the various stages of this process. Here, we show that in response to TGF-beta, phosphorylated Smads rapidly translocated into the nucleus and activated transcription of target genes such as E-cadherin repressors of the Snail superfamily, causing loss of cell adhesion. Within the TGF-beta superfamily of cytokines, TGF-beta1, -beta2 and -beta3 were specific for the induction of hepatocellular EMT. Expression profiling of EMT kinetics revealed 78 up- and 235 downregulated genes, which preferentially modulate metabolic activities, extracellular matrix composition, transcriptional activities and cell survival. Independent of the genetic background, platelet-derived growth factor (PDGF)-A ligand and both PDGF receptor subunits were highly elevated, together with autocrine secretion of bioactive PDGF. Interference with PDGF signalling by employing hepatocytes expressing the dominant-negative PDGF-alpha receptor revealed decreased TGF-beta-induced migration in vitro and efficient suppression of tumour growth in vivo. In conclusion, these results provide evidence for a crucial role of PDGF in TGF-beta-mediated tumour progression of hepatocytes and suggest PDGF as a target for therapeutic intervention in liver cancer.

Animals↗

PubMed2006

[Muscle and tendon injuries of the knee joint].

Muscles and tendons contribute greatly to stabilization of the knee joint and are crucial elements for normal joint function. Therefore, injuries of those structures cause variable degrees of disability, depending on the severity of the lesion. Due to the characteristic structural changes and alterations of signal intensities, MR imaging allows accurate identification and staging of acute injuries of muscles and tendons, as well as assessment of chronic or degenerative disease. The knowledge of anatomy and normal function of muscles and tendons, together with a thorough understanding of the mechanism and usual combinations of their injuries (e.g., posterolateral structures) allows an exact evaluation of injury-induced functional impairments to the knee joint. A detailed and exact radiological report is of the greatest importance for the referring clinician and the patient to determine optimal therapeutic strategies.

Humans↗

PubMed2006

[MRI after meniscus and cruciate ligament surgery].

Nowadays, due to its high diagnostic accuracy, MR imaging is the method of choice for the evaluation of knee joint disorders pre- and postoperatively. Accurate diagnosis is sometimes possible only if the reporting radiologist has knowledge of the therapeutic procedures and the surgical report. Frequently, further therapeutic management is strongly influenced by MR examinations and radiological reports.

Anterior Cruciate Ligament↗

PubMed2005

[Nursing care assessment and decubitus ulcer. A data evaluation of nursing care in the MDK-WL].

PURPOSE: To detect the frequency and circumstances of sore ulcers in comparatively unselected patients of the German nursing care insurance who claimed for compensation. Setting Cross-sectional/case-control. METHODS: Data sampling and descriptive analysis. Assembled data were biometric data, level of the need of care, grade of sore ulcer, duration of sore ulcer, bedding materials and frequency of wound dressings of sore ulcer. RESULTS: In 97 622 out-patients and 32 059 patients from nursing care units, there were 3.2 and 6.4% sore ulcers, respectively, with diverse grades of severity present. Despite the difference in frequency of sore ulcers, no distinction in the nursing quality could be shown between out-patients and patients from nursery care units. Our data possibly suggested a lack with regard to evidence-based prophylaxis and treatment of sore ulcers in both groups. CONCLUSIONS: For both out-patients and patients from nursing care units, prophylaxis and treatment of sore ulcers could possibly be improved. Further studies will be needed to reveal the short-comings in nursing-care and to map out strategies for improvement.

Aged↗

PubMed2003

The Zurich Study: participation patterns and Symptom Checklist 90-R scores in six interviews, 1979-99.

OBJECTIVE: The Zurich study is a longitudinal study in psychiatric epidemiology that started in the late 1970s. The sixth interview in 1999 provides the basis to investigate and update the participation and drop-out patterns of the Zurich subjects. METHOD: Aside from descriptive analyses, particular attention was paid to the Symptom Checklist 90-R (SCL-90-R), used initially to stratify the Zurich sample. RESULTS: The initial proportions of high-scorers vs. low-scorers (two-thirds vs. one-third) have not changed significantly in the 367 subjects who participated in the 1999 interview. More detailed analyses indicate a selective and changing dependence of participation/drop-out on health status as measured by the SCL-90 R. In recent interviews drop-out has become more likely in subjects with extremely high SCL scores and in subjects with low SCL scores. CONCLUSION: Drop-out in the Zurich Study is associated with extreme SCL scores.

Adult↗

PubMed2003

Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves' disease.

Autoimmune thyroid diseases are thought to be mediated by pro-inflammatory cytokines such as TNFalpha and IL-6. Serum levels of cytokines may indicate activity levels of immune functions. We investigated serum levels of IL-6 and of the soluble receptor of TNFalpha in patients with newly diagnosed onset of Graves' hyperthyroidism. The predominantly female group consisted of 39 patients, mean fT4 was 47.6 pg/ml (normal values 7.5=19.0 pg/ml). After diagnosis, all patients were treated with anti-thyroid drugs. Soluble Tumour Necrosis Factor Receptor I (TNF-RI) serum levels were found significantly increased (mean 3.7+/-1.3 ng/ml; p<0,01) compared to a matched group of apparent healthy individuals (mean sTNF-RI 1.8+/-0.5 ng/ml) and to a matched group of patients with treated Graves' disease (mean sTNF-RI 1.9+/-0.6 ng/ml). When IL-6 was assessed only 4 of the 39 patients exhibited increased serum levels. Our finding may indicate that sTNF-RI and possibly its ligand, TNFalpha, could play an important role in the onset of the acute stage of Graves' disease.

Adult↗

PubMed2002

Ascent of dinosaurs linked to an iridium anomaly at the Triassic-Jurassic boundary.

Analysis of tetrapod footprints and skeletal material from more than 70 localities in eastern North America shows that large theropod dinosaurs appeared less than 10,000 years after the Triassic-Jurassic boundary and less than 30,000 years after the last Triassic taxa, synchronous with a terrestrial mass extinction. This extraordinary turnover is associated with an iridium anomaly (up to 285 parts per trillion, with an average maximum of 141 parts per trillion) and a fern spore spike, suggesting that a bolide impact was the cause. Eastern North American dinosaurian diversity reached a stable maximum less than 100,000 years after the boundary, marking the establishment of dinosaur-dominated communities that prevailed for the next 135 million years.

Animals↗

PubMed2002

Evaluation of pituitary microadenomas with dynamic MR imaging.

PURPOSE: To evaluate the use of keyhole dynamic magnetic resonance (MR) imaging in the evaluation of women with borderline hyperprolactinemia. PATIENTS AND METHODS: We investigated 30 patients (mean age 31.6+/-4.3 years) with moderate hyperprolactinemia and clinically suspected microadenomas on T1-weighted spin echo (SE) sequences (repetition time (TR)/echo time (TE) 625/15 ms) with keyhole dynamic imaging and contrast enhancement of the pituitary gland. The probability of lesion presence according to MR criteria was ranked on a five-grade scale and compared with standard examinations of the hypophysis before and after intravenous administration of contrast media. RESULTS: The probability for lesion presence showed a trend toward lower scores on standard SE sequences and higher scores with dynamic imaging (P=0.067). CONCLUSION: Dynamic keyhole imaging of the pituitary gland could help establish a diagnosis of microadenomas with a higher probability.

Adenoma↗

PubMed2002

Intermittent weekly high-dose capecitabine in combination with oxaliplatin: a phase I/II study in first-line treatment of patients with advanced colorectal cancer.

BACKGROUND: The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of an intermittent weekly capecitabine regimen in combination with oxaliplatin. Furthermore, we intended to explore its safety at the recommended dose, and to assess its principal antitumor activity in patients with advanced colorectal cancer. PATIENTS AND METHODS: Thirty patients with measurable metastatic colorectal cancer who previously were unexposed to palliative chemotherapy were enrolled on to this disease-oriented phase I trial. They were treated with a fixed dose of oxaliplatin (85 mg/m(2) administered as a 2-h intravenous infusion on day 1) plus escalating doses of capecitabine (given at two divided daily doses from days 1 to 7), repeated every 2 weeks. The dose of oral fluoropyrimidine was escalated in consecutive cohorts of three to six patients from 2500 to 4000 mg/m(2)/day. After having defined the toxic dose, nine additional patients were entered at the MTD/recommended dose to confirm its safety profile, and assure suitability for future phase II/III studies. RESULTS: In the phase I part of the study, 21 patients were enrolled, and a total of 222 courses were administered through four dose levels of capecitabine combined with oxaliplatin 85 mg/m(2). Gastrointestinal toxicities, predominantly diarrhea, were the principal DLTs. Other severe adverse events included grade 3 asthenia, acute neurological symptoms and skin toxicity. The combination was not myelosuppressive, eliciting only sporadically grade 3/4 neutropenia and/or thrombocytopenia. There was no alopecia, and only a few patients experienced mild symptoms of hand-foot syndrome. Externally reviewed objective responses were noted in 15 of all 30 evaluable patients (overall response rate, 50%; 95% confidence interval 31% to 69%) including three complete remissions and median progression-free survival was 8.8 months (range 7-14+ months). CONCLUSIONS: Overall results of this study indicate that the administration of clinically relevant single-agent doses of both capecitabine and oxaliplatin is feasible and seems to result in promising therapeutic activity in patients with advanced colorectal cancer. On the basis of the toxicological profile of the combination regimen shown in the present study, oxaliplatin 85 mg/m(2) as a 2-h intravenous infusion every 2 weeks administered in combination with capecitabine 3500 mg/m(2)/day x7 in two divided doses is recommended for further evaluations.

Administration, Oral↗

PubMed2002

The impact of hemoglobin levels on fatigue and quality of life in cancer patients.

BACKGROUND: Although fatigue is a commonly reported symptom in cancer patients its etiology is still poorly understood. The objective of the present study was to investigate the relationship between hemoglobin (Hb) levels and the subjective experience of fatigue and quality of life in cancer patients with mild or no anemia undergoing chemotherapy. PATIENTS AND METHODS: Sixty-eight cancer patients (25 colorectal, 26 lung and 17 ovarian cancer) presently undergoing chemotherapy participated in the study. Fatigue was measured with the Multidimesional Fatigue Inventory (MFI-20), quality of life with The European Organization for Research and Treatment of Cancer QLQ-C30. In order to provide normative data for fatigue levels, the MFI-20 was also completed by a sex- and age-matched sample of 120 healthy controls. RESULTS: Compared with healthy subjects, cancer patients experienced significantly higher levels of subjective fatigue. Correlations between Hb values and subscales of the MFI-20 were moderate with a tendency to increase during chemotherapy. Hb values alone, however, do not fully account for the observed fatigue. Other symptoms, especially pain, dyspnea and sleep disturbances, also showed an association with perceived fatigue. CONCLUSIONS: Despite significant correlations, these results indicate that Hb values only partially explain subjectively experienced fatigue and quality of life in cancer patients. It is suggested therefore that the treatment of fatigue must be multidimensional and involve all areas which contribute to the syndrome.

Adult↗

PubMed2002

Avascular necrosis after osteotomy of the talar neck to correct residual club-foot deformity in children. A long-term review.

In order to determine the incidence of avascular necrosis after osteotomy of the talar neck, we re-evaluated 11 patients (16 feet) with idiopathic club foot who had undergone this procedure at a mean age of eight years (5 to 13) to correct a residual adduction deformity. All had been initially treated conservatively and operatively. The mean follow-up was 39 years (36 to 41). Surgery consisted of a closing-wedge osteotomy of the talar neck combined, in 14 feet, with lengthening of the first cuneiform and a Steindler procedure. At follow-up eight feet were free from pain, three had occasional mild pain and five were regularly painful after routine activities. Two patients were unlimited in their activity, six occasionally limited after strenuous and three regularly limited after strenuous activity. Using the Ponseti score, the feet were rated as good in four, fair in three and poor in nine. In seven feet avascular necrosis with collapse and flattening of the talar dome had occurred. In all of these feet the children were younger than ten years of age at the time of surgery. In three feet, avascular necrosis of the talar head was also observed. We conclude that osteotomy of the talar neck in children under the age of ten years can cause avascular necrosis and should be abandoned.

Adolescent↗

PubMed2001

[Is there progress in chemotherapy for breast cancer?].

Breast cancer is the most frequent type of cancer in women. The therapeutic approaches to breast cancer have developed rapidly over the past 20 years, due to the increasing knowledge about the biology of breast cancer. Therefore it was possible to increase response rates as well as the duration of response and survival in neoadjuvant, adjuvant, and palliative treatment. This paper gives a review of the current breast cancer trials. Effective new cytotoxic chemotherapy and hormonal therapy agents, as well as the identification of specific molecular abnormalities (HER2/neu) led to the development of targeted therapeutic interventions in the neoadjuvant, adjuvant, and palliative treatment of breast cancer. Increased understanding of the biology of breast cancer led to the development of rational therapeutic interventions, which are currently under active clinical development.

Algorithms↗

PubMed2001

Enterovirus infection--a possible trigger for Graves' disease?

Viruses are potential environmental factors in autoimmune disease. Some evidence suggests a relationship between enteroviral infection (especially Coxsackie B virus) and autoimmunity. We investigated 21 individuals with recent onset of Graves' hyperthyroidism in regard of (subclinical) enterovirus infection. Thyrotoxic symptoms had started about two months before blood sample collection. The patients were from Upper Austria and mainly female (17/21). Their mean free thyroxin levels in blood were twice the maximum normal value and the majority achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We employed a nested PCR reaction with primers of the enterovirus genome on blood samples. All were negative for RNA of the enterovirus group. Coxsackie and related viruses were not identified as a trigger factor in autoimmune thyrotoxic disease.

Adult↗

PubMed2001

Absence of clonal chromosomal relationship between concomitant B-CLL and multiple myeloma--a report on two cases.

B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) are chronic B-cell malignancies that represent different stages of B-cell maturation. Occasionally, both diseases are present in the same patient, and this raises the question of clonal associations between the two neoplasms. We here report on two patients with concomitant B-CLL and MM. Clonal chromosomal abnormalities in both lymphocytic cells and plasma cells were studied by interphase fluorescence in situ hybridization (FISH) using a panel of 24 chromosome- and region-specific DNA probes. In the first patient, cytogenetics revealed 47, X, t(Y;22)(p11;q10), +12, dell4(q21q32). By FISH, +12 was present in lymphoid cells, but not in plasma cells. MM cells were characterized by multiple chromosomal gains (1, 11q23) and losses (5q, 10, 13q14, 15, 17p13, Y), which were all undetectable in lymphoid cells. The second patient, in whom no clonal abnormalities were obtained by conventional cytogenetic analysis, had lymphoid cells with loss of 8q24 by FISH. In contrast, evidence for a gain of 8q24 (consistent with amplification of c-myc) was obtained in 13% of plasma cells. Plasma cells were further characterized by gains of chromosomes 1, 3, 11, 18, and Y. We thus conclude that this comprehensive molecular cytogenetic analysis demonstrates the existence of two clonally distinct B-cell malignancies in both patients.

Aged↗

PubMed2001

Advances in the biology and therapeutic management of multiple myeloma.

During the past decade, new developments have increased our understanding of the biological features of multiple myeloma (MM), and novel therapeutic approaches have improved the outcome and quality of life. The importance of both the malignant clone and the bone marrow environment for disease evolution and propagation has been recognized, and therapeutic approaches that target both components of the disease process appear to be most promising. Along this line, thalidomide has been observed to exert activity in chemotherapy-refractory MM and thus expands the therapeutic armamentarium against MM. Use of high-dose melphalan with autologous stem cell transplantation has resulted in an improved rate of complete remissions as well as prolonged event-free and overall survival. Novel treatment strategies exploiting anti-myeloma immunity (nonmyeloablative allogeneic transplantation, vaccination) are being investigated and carry the potential to further improve the outcome of patients with MM.

Humans↗

PubMed2001

Angiogenic profile of childhood primitive neuroectodermal brain tumours/medulloblastomas.

Primitive neuroectodermal brain tumours (PNET) including medulloblastomas (PNET/MB) are the most common malignant brain tumours of childhood. Similar to many other brain tumours, PNET/MB often show marked neovascularisation. To determine which angiogenic factors contribute to PNET/MB angiogenesis, we examined the expression of eight angiogenic factors (vascular endothelial growth factors (VEGF, VEGF-B, VEGF-C), basic fibroblast growth factor (bFGF), angiopoetins (Ang-1, Ang-2), transforming growth factor (TGF-alpha), and platelet-derived endothelial growth factor (PDGF-A)) by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in six PNET cell lines and 28 primary PNET/MB. Expression levels of angiogenic factors were compared with microvessel density, TrkC mRNA expression, clinical variables and survival outcomes. Our results indicate that all PNET/MB tested produce a wide range of angiogenic factors that are, individually or together, likely to play a direct role in PNET/MB tumour growth. This suggests that anti-angiogenesis approaches targeting VEGF alone may be insufficient in PNET/MB.

Adolescent↗

PubMed2001

Bacterial origin for the isoprenoid biosynthesis enzyme HMG-CoA reductase of the archaeal orders Thermoplasmatales and Archaeoglobales.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase or HMGR) fulfills an essential role in archaea, as it is required for the synthesis of isoprenoid ethers, the main component of archaeal cell membranes. There are two clearly homologous but structurally different classes of the enzyme, one found mainly in eukaryotes and archaea (class 1), and the other found in bacteria (class 2). This feature facilitated the identification of several cases of interdomain lateral gene transfer (LGT), in particular, the bacterial origin for the HMGR gene from the archaeon Archaeoglobus fulgidus. In order to investigate if this LGT event was recent and limited in its scope or had a broad and long-term impact on the recipient and its related lineages, the HMGR gene was amplified and sequenced from a variety of archaea. The survey covered close relatives of A. fulgidus, the only archaeon known prior to this study to possess a bacterial-like HMGR; representatives of each main euryarchaeal group were also inspected. All culturable members of the archaeal group Archaeoglobales were found to display an HMGR very similar to the enzyme of the bacterium Pseudomonas mevalonii. Surprisingly, two species of the genus Thermoplasma also harbor an HMGR of bacterial origin highly similar to the enzymes found in the Archaeoglobales. Phylogenetic analyses of the HMGR gene and comparisons to reference phylogenies from other genes confirm a common bacterial origin for the HMGRs of Thermoplasmatales and Archaeoglobales. The most likely explanation of these results includes an initial bacteria-to-archaea transfer, followed by a another event between archaea. Their presence in two divergent archaeal lineages suggests an important adaptive role for these laterally transferred genes.

Archaeoglobales↗