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Biomedical subjects

H Huber

Publications and source records attributed to H Huber.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Primary lymphoma of the thyroid with contralateral recurrence--case report].

Primary lymphomas located in the thyroid gland are rare clinical findings. The therapy and the subsequent monitoring of the disease continue to be a subject of debate. We present the case of a 63-year-old female patient in whom a hemi-thyroidectomy was performed because of a growing goiter. Histological examination of the excised tissue revealed a large-cell B-lymphocytic lymphoma which extended to neighboring lymph nodes. The patient received chemotherapy which led to remission of disease for two years. The disease re-occurred in the remaining thyroid lobe. Subsequently, the patient was treated with involved-field radiation therapy which lead to long term remission. We conclude that total thyroidectomy should be considered in the treatment of lymphomas located in the thyroid gland.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The unusual iron sulfur composition of the Acidianus ambivalens succinate dehydrogenase complex.

The succinate dehydrogenase complex of the thermoacidophilic archaeon Acidianus ambivalens was investigated kinetically and by EPR spectroscopy in its most intact form, i.e., membrane bound. Here it is shown that this respiratory complex has an unusual iron-sulfur cluster composition in respect to that of the canonical succinate dehydrogenases known. The spectroscopic studies show that center S3, the succinate responsive [3Fe-4S]1+/0 cluster of succinate dehydrogenases, is not present in membranes prepared from aerobically grown A. ambivalens, nor in partially purified complex fractions. On the other hand, EPR features associated to the remaining centers, clusters S1 ([2Fe-2S]1+/2+) and S2 ([4Fe-4S]2+/1+), could be observed. Similar findings were made in other archaea, namely Acidianus infernus and Sulfolobus solfataricus. Kinetic investigations showed that the A. ambivalens enzyme is reversible, capable of operating as a fumarate reductase - a required activity if this obligate autotroph performs CO2 fixation via a reductive citric acid cycle. Sequencing of the sdh operon confirmed the spectroscopic data. Center S3 ([3Fe-4S]) is indeed replaced by a second [4Fe-4S] center, by incorporation of an additional cysteine, at the cysteine cluster binding motif (CxxYxxCxxxC-->CxxCxxCxxxC). Genomic analysis shows that genes encoding for succinate dehydrogenases similar to the ones here outlined are also present in bacteria, which may indicate a novel family of succinate/fumarate oxidoreductases, spread among the Archaea and Bacteria domains.

Amino Acid Sequence↗
PubMed1999

Hyperdiploidy and apparent aneusomy in mesothelial cells from non-malignant effusions as detected by fluorescence in situ hybridization (FISH).

Interphase cytogenetics by fluorescence in situ hybridization (FISH) can be used to detect malignant cells characterized by chromosomal aneuploidy. However, apparent aneusomy in normal "control" tissues has to be considered when using FISH as diagnostic tool. In effusions as model tissue exposed to metastasis, the definition of cut-off levels for background aneusomy by FISH was aimed in this study. Using centromeric probes representing chromosomes 7, 8, 11, 12, 17 and 18, extensive chromosome copy number enumeration by single-color FISH analysis was performed in pleural and ascitic effusions derived from 15 patients with various, non-malignant diseases. In all effusions, cells with gain of hybridization signals for several or all chromosomes tested were found (in up to 1.94% of cells). A consistent finding was high grade hyperdiploidy (>4 centromeric signals). Mesothelial elements mainly contributed to hyperdiploidy in effusions, as demonstrated by a combined analysis of FISH and immunocytochemistry with staining for cytokeratin. Dual-color FISH analysis showed that hyperdiploidy was predominantly corresponding to polyploidization; however, there were always minor cell populations classified as aneuploid by dual-color FISH. In conclusion, stringent criteria have to be applied to distinguish malignancy-related aneuploidy from background aneusomy by FISH.

Adult↗
PubMed1999

Advanced non-small-cell lung cancer: adjunctive interferon gamma in induction and maintenance therapy.

PURPOSE: To evaluate the feasibility of interferon gamma (IFNgamma) as an adjunct to chemotherapy in advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 32 patients were recruited and received 25 mg/m2 cisplatin and 100 mg/m2 etoposide on days 8, 10 and 12 every 3 weeks for a total of three cycles. A dose of 100 microg IFNgamma was given subcutaneously three times weekly from days 1 to 8 and between days 15 and 29. After induction, all patients except those with progressive disease were offered IFNgamma maintenance therapy: 100 microg three times weekly. RESULTS: The following responses were obtained: partial response, 5 (16%); minor response, 12 (37%); stable disease, 4 (13%); progressive disease, 11 (34%). The survival rates after 1 and 2 years were 47% and 25% respectively. Patients receiving maintenance IFNgamma had a 2-year survival rate of 58%. Toxic side-effects were rare and included grade III/IV fever (7%/1%) and grade III/IV leucopenia (4%/1%). CONCLUSIONS: In patients with advanced NSCLC, an adjunctive dose of 100 microg IFNgamma, given three times weekly in the induction and maintenance phase, is feasible. Survival data seem favourable so this regimen may warrant further investigation in a phase III study.

Adult↗
PubMed1999

The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model.

OBJECTIVE: Organ transplantation is limited by the number of brain-dead human donors. Xenotransplantation could be an alternative to guarantee a constant supply of organs. A major problem of xenotransplantation are xenogeneic natural antibodies (XNAb) directed against species-specific antigens of a discordant donor species (e.g. pig). They trigger the hyperacute xenograft rejection (HXR). Re-usable immunoapheresis (LA)-columns Ig-Therasorb (Therasorb, Baxter) were used to adsorb these XNAb. The effect of immunoapheresis of the perfusing human blood was investigated in ex vivo working pig hearts. METHODS: Hearts of 12 landrace pigs (body weight 14-31 kg) were explanted after inducing cardiac arrest with 4 degrees C Celsior solution. Human blood (500 ml, heparinized) was obtained from healthy volunteers. In group 1 (G1, n = 6), blood as perfusate remained untreated. In group 2 (G2, n = 6), native blood was separated by plasmapheresis into cellular components and plasma. The latter passed through the Ig-Therasorb column for removal of immunoglobulins (so-called immunoadsorption or immunoapheresis). After back-table preparation the hearts were mounted to the working heart model. After 20 min of reperfusion in Langendorff mode, the working heart mode was established. Blood samples were taken isochronously for measurement of: CK(-MB), LDH, ASAT, troponin, immunoglobulins, complement activity, anti-pig antibodies and others. After cessation of the heart, atrial and ventricular tissue samples were taken for histological examinations (light/electron microscopy and immunohistochemistry). RESULTS: Two cycles of immunoapheresis reduced the levels of IgG by 84%, IgM by 83.3% and IgA by 76%. In G2, the antibody immunoadsorption of blood prolonged the duration of the working heart mode significantly to 335+/-37.5 min. In contrast, hearts of group 1 (control) failed after 125+/-31.3 min. Heart rate was significantly different between both groups (G1, 77.3+/-6.1 beats/min; G2, 86.5+/-5.5 beats/min). In G2 cardiac output was 118% and mean coronary flow was 154.6% higher than in G1. CK, LDH and ASAT showed no differences in the two groups. Heart weight increased significantly more in group 1 than in G2. Histological examination indicated specific signs of HXR in G1 after 1.5 h, whereas in G2 only slight unspecific damages were found after 6 h. CONCLUSION: Antibody removal by means of immunoapheresis results in a significantly improved xenogeneic cardiac function. Immunoapheresis may, therefore, become an important adjunct in future pig-to-man clinical xenotransplantation.

Animals↗
PubMed1999

Effects of prolonged cold storage time in xenotransplantation.

BACKGROUND: Ischemia and reperfusion injury after prolonged ischemic time (IT) has a marked influence on hyperacute xenograft rejection (HXR). The aim of the study was to investigate the impact of different cold ischemic times on the HXR of ex vivo "working pig hearts" perfused with human blood. Xenoreactive natural antibodies (XNAb) as the trigger of HXR were reduced by immunoadsorption (IA) using an Ig-Therasorb column. METHODS: Hearts of 24 Landrace pigs (13-31 kg) were harvested after cardioplegia with Celsior-solution and split into 4 groups. In Group C1 (n = 6) the short ischemic time (IT) lasted 48.9+/-10 minutes on the average prior to start of xenoperfusion, in Group I1 IT lasted 4 hours instead. Groups C2 and 12 experienced the same IT as C1 and I1, respectively, but underwent 2 cycles of IA in addition. IA removed immunoglobulins IgG, IgM and IgA from the perfusate. In the working heart mode hemodynamic parameters were measured in defined intervals. Blood samples were collected at the same time to determine myocardial enzymes, immunoglobulins, complement and anti-pig-antibodies. At the end of the study (cardiac arrest) tissue was sampled for histologic examination (light/electron microscopy (LM/EM) and immunohistochemistry). RESULTS: Survival time of the control Group C1 was 125 minutes. IA resulted in an extension of perfusion time to 6.5 hours in C2. Four hours of IT (I1) prolonged the working time of hearts when compared with C1. IA had no additional impact (I2). Heart weight increased significantly in C1 without IA. Cardiac output and coronary flow in C1 were significantly lower when compared with the other 3 groups. IA improved cardiac output (CO) in C2 (vs C1, p < 0.001). Histologic signs of HXR (LM/EM) could be found in C1 in contrast to the other groups. Serologic parameters for myocardial damage were higher in groups with prolonged IT than in groups with short IT. CONCLUSION: Prolonged ischemia and reperfusion injury showed controversial effects in this specific xenogeneic heart transplant model. In contrast to observations in allogeneic transplantation 4 hours of IT showed a beneficial behaviour of the xenografts. Reasons could be either a protective effect of the Celsior solution or changes of the endothelial cell surface (in terms of glycosylation or loss of alpha1-3Gal-epitopes). Tolerance of prolonged IT would allow transportation of xenografts over long distances.

Animals↗
PubMed1999

Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c-erbB and retinoic acid receptor expression in MCF-7 breast cancer cells.

Nuclear steroid/thyroid/retinoid receptors and c-erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c-erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross-connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c-erbB-2, and between ER and retinoic acid receptor(RAR)-alpha have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12-O-tetradecanoylphorbol-13-acetate, TPA), on growth and expression of c-erbB and RARs in MCF-7 breast cancer cells, which contain high levels of RAR-alpha and -gamma, and which express significant amounts of c-erbB-2 and -3. All trans-retinoic acid (tRA), the anti-estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17beta-estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c-erbB-2 and -3, whereas tamoxifen, Forsk and TPA up-regulated c-erbB-2. c-erbB-3 was co-regulated with c-erbB-2. Northern analysis demonstrated that RAR-alpha was down-regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up-regulated RAR-alpha. RAR-gamma expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c-erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.

Blotting, Northern↗
PubMed1999

Treatment of small cell lung cancer patients.

Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure.

Antineoplastic Agents↗
PubMed1999

[Short-term follow-up of a series of 21 uncemented total ankle prostheses].

GOALS OF THE STUDY: To analyse the short term results of 21 non cemented meniscal-bearing total ankle arthroplasties. MATERIAL AND METHODS: [corrected] 21 ankle arthroplaties were performed in 21 patients with a mean age of 63.5 years. Diagnoses include primary and post-traumatic osteoarthritis. Our mean follow-up is 21 months. RESULTS: We evaluated the patients with the Koefod ankle score. We present only the results of the patients whose follow-up exceed one year. Eleven patients had an excellent result, seven a good and two a medium result. One case was a failure and needed an arthrodesus. DISCUSSION: The non-cemented meniscal-bearing ankle prosthesis leads to good relieve of pain and good function but fair improvement of the mobility. These first results are encouraging but definitive conclusions cannot be drawn yet.

Adult↗
PubMed1999

Nucleoid structure and partition in Methanococcus jannaschii: an archaeon with multiple copies of the chromosome.

We measured different cellular parameters in the methanogenic archaeon Methanococcus jannaschii. In exponential growth phase, the cells contained multiple chromosomes and displayed a broad variation in size and DNA content. In most cells, the nucleoids were organized into a thread-like network, although less complex structures also were observed. During entry into stationary phase, chromosome replication continued to termination while no new rounds were initiated: the cells ended up with one to five chromosomes per cell with no apparent preference for any given DNA content. Most cells in stationary phase contained more than one genome equivalent. Asymmetric divisions were detected in stationary phase, and the nucleoids were found to be significantly more compact than in exponential phase.

Cell Cycle↗
PubMed1999

In vivo observation of cell division of anaerobic hyperthermophiles by using a high-intensity dark-field microscope.

To study growth and cell division of anaerobic hyperthermophilic archaea in vivo, a cultivation technique using glass capillaries was developed. At temperatures of 90 to 98 degrees C, at least 10 successive cell divisions of Pyrodictium abyssi TAG 11 were documented. Cells divide by binary fission. Visualized under a modified dark-field microscope, the formation of cannulae, which finally connected all cells, was observed. The cannulae elongated at 1.0 to 1.5 micrometers/min and reached final lengths of between 30 and 150 micrometers. A "snapping division"-like mode of cell fission was discovered for Thermoproteus tenax.

Anaerobiosis↗
PubMed1999

Presence of acetyl coenzyme A (CoA) carboxylase and propionyl-CoA carboxylase in autotrophic Crenarchaeota and indication for operation of a 3-hydroxypropionate cycle in autotrophic carbon fixation.

The pathway of autotrophic CO2 fixation was studied in the phototrophic bacterium Chloroflexus aurantiacus and in the aerobic thermoacidophilic archaeon Metallosphaera sedula. In both organisms, none of the key enzymes of the reductive pentose phosphate cycle, the reductive citric acid cycle, and the reductive acetyl coenzyme A (acetyl-CoA) pathway were detectable. However, cells contained the biotin-dependent acetyl-CoA carboxylase and propionyl-CoA carboxylase as well as phosphoenolpyruvate carboxylase. The specific enzyme activities of the carboxylases were high enough to explain the autotrophic growth rate via the 3-hydroxypropionate cycle. Extracts catalyzed the CO2-, MgATP-, and NADPH-dependent conversion of acetyl-CoA to 3-hydroxypropionate via malonyl-CoA and the conversion of this intermediate to succinate via propionyl-CoA. The labelled intermediates were detected in vitro with either 14CO2 or [14C]acetyl-CoA as precursor. These reactions are part of the 3-hydroxypropionate cycle, the autotrophic pathway proposed for C. aurantiacus. The investigation was extended to the autotrophic archaea Sulfolobus metallicus and Acidianus infernus, which showed acetyl-CoA and propionyl-CoA carboxylase activities in extracts of autotrophically grown cells. Acetyl-CoA carboxylase activity is unexpected in archaea since they do not contain fatty acids in their membranes. These aerobic archaea, as well as C. aurantiacus, were screened for biotin-containing proteins by the avidin-peroxidase test. They contained large amounts of a small biotin-carrying protein, which is most likely part of the acetyl-CoA and propionyl-CoA carboxylases. Other archaea reported to use one of the other known autotrophic pathways lacked such small biotin-containing proteins. These findings suggest that the aerobic autotrophic archaea M. sedula, S. metallicus, and A. infernus use a yet-to-be-defined 3-hydroxypropionate cycle for their autotrophic growth. Acetyl-CoA carboxylase and propionyl-CoA carboxylase are proposed to be the main CO2 fixation enzymes, and phosphoenolpyruvate carboxylase may have an anaplerotic function. The results also provide further support for the occurrence of the 3-hydroxypropionate cycle in C. aurantiacus.

Acetyl Coenzyme A↗
PubMed1999

Type 1 diabetes mellitus and oral health: assessment of periodontal disease.

BACKGROUND: The periodontal disease status of 320 dentate adults, diagnosed 23.7 years previously with Type 1 insulin dependent diabetes mellitus, was evaluated. These patients had been monitored at 2-year intervals as part of a large University of Pittsburgh longitudinal study assessing the medical complications associated with insulin dependent diabetes. METHODS: During one of their regularly scheduled medical examinations, a group of 320 adult dentate subjects (mean age of 32.1 years) received a periodontal examination as part of a comprehensive oral health assessment. The oral health assessment collected data regarding demographics, oral health behaviors, tooth loss, coronal and root caries, salivary functions, and soft tissue pathologies. For the periodontal assessments, 3 facial sites (mesial, midcervical, distal) of the teeth in the right maxillary/left mandibular or left maxillary/right mandibular quadrants were evaluated for calculus, bleeding on probing (BOP) and loss of gingival attachment (LOA). RESULTS: Attachment loss was significantly greater for older patients whereas BOP and calculus levels were relatively constant across age categories. Univariate analyses of factors possibly related to extensive periodontal disease (LOA > or =4 mm for at least 10% of sites examined) indicated an association with older age; lower income and education; past and current cigarette smoking; infrequent visits to the dentist; tooth brushing less than once per day; older age of onset; longer duration of diabetes; and the diabetic complication of neuropathy. A multivariate regression model of all possibly significant factors found current cigarette use (odds ratio [OR] = 9.73), insulin dependent diabetes onset after 8.4 years of age (OR = 3.36), and age greater than 32 years (OR = 3.00) explained the majority of the extensive periodontal disease in this group of diabetic patients. CONCLUSIONS: Management and prevention of extensive periodontal disease for Type 1 diabetic patients should include strong recommendations to discontinue cigarette smoking.

Adult↗
PubMed1999

[Salivary cortisol as a stress parameter in piglets].

The relationship between salivary and plasma levels of total and free cortisol was monitored in 97 male piglets, aged two to four weeks, subjected to castration. Samples were taken 10 minutes before (basal value) as well as one, two, three, four and 24 hours post castration and at the same time intervals from a control group of 17 animals which did not undergo surgery. Simultaneously to blood (indwelling catheter) withdrawing saliva was collected by two cotton swabs. Cortisol levels were measured by radioimmunoassay (RIA). A highly significant increase in total, free and salivary cortisol was found within the first four hours after castration compared to the control group. The percentage increase one hour after castration above basal values was highest in free plasma cortisol (21.08 +/- 2.03 nmol/l vs. 61.26 +/- 4.16 nmol/l; 290.6%), and lowest in total plasma cortisol (177.33 +/- 9.69 nmol/l vs. 374.09 +/- 18.21 nmol/l; 211.0%), whereas salivary cortisol showed an 255.7% increase (10.46 +/- 1.03 nmol/l vs. 26.75 +/- 1.93 nmol/l). Total cortisol included 11.9-16.4% free cortisol. Salivary cortisol concentration was between 5.9% and 7.5% of the total plasma cortisol concentration. The highest correlation between total plasma cortisol and salivary cortisol occurred one hour after castration (r = 0.57; p < 0.01). The correlation between free and salivary cortisol was lowest for basal values (r = 0.27; p < 0.05), whereas correlations for the remaining time points were highly significant (0.41 < or = r < or = 0.61; p < 0.01). For the control group significant correlations were found between salivary and total plasma cortisol (0.58 < or = r < or = 0.89; p < 0.05) and between free and salivary cortisol (0.63 < or = r < or = 0.92; p < 0.05). The present work indicates that the measurement of salivary levels of cortisol reflects the concentration of this hormone in plasma samples of piglets.

Animals↗
PubMed1999

Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma.

Expression of the lung resistance protein (LRP) is associated with resistance to various anticancer drugs including melphalan and, therefore, may affect the clinical outcome in multiple myeloma (MM). To determine the clinical significance of LRP, we have compared LRP expression in bone marrow plasma cells with clinical parameters including response to chemotherapy and survival of previously untreated patients with MM (n = 72). LRP expression immunocytochemically assessed by means of the LRP-56 monoclonal antibody was positive (> or =10% staining plasma cells) in 44 (61%) samples. There was no correlation between LRP expression and age, sex, type of the paraprotein, serum creatinine, stage, beta2-microglobulin, serum lactate dehydrogenase, or C-reactive protein. However, LRP expression was more frequently observed in patients with a p53 deletion than in those without such a deletion (P = 0.01). The overall response rate for all of the patients evaluable for response to induction chemotherapy (n = 58) was 67%. The response rate was 87% for patients without LRP expression but only 54% for patients with LRP expression (P = 0.01). Kaplan-Meier analysis revealed that patients with LRP expression had a shorter overall survival (median, 33 months) than those without LRP expression (median not reached; P = 0.04). These data show that LRP expression is an important marker for clinical drug resistance and predicts a poor outcome in MM.

Adult↗
PubMed1999

[Fundamentals and results of cytostatic chemotherapy in some of the most common solid tumors].

In this review we discuss established cytostatic chemotherapies as well as developments and perspectives for the three most common tumour entities. Adjuvant and neoadjuvant therapy models for primary breast cancer are discussed, established and newer concepts in palliative care presented and open questions about high dose chemotherapy raised, which need to be settled before their routine use. Developments in the field of lung cancer therapy such as adjuvant and neoadjuvant approaches are pointed out and the importance of multimodal and interdisciplinary treatment modalities is underlined. Newer cytostatic drugs are compared with established agents. In the field of colorectal cancer several new thymidilatsynthase-inhibitors as well as drugs with different mode of action are available. With these new agents, [table: see text] cytostatic therapy of advanced stages and most probably also in the adjuvant setting could markedly be improved.

Antineoplastic Agents↗