PubMed Health⌕ Search

Biomedical subjects

M Hermann

Publications and source records attributed to M Hermann.

At least 37 records · Page 2Linked to original sources
PubMed2002

Determination of molecules regulating gene delivery using adenoviral vectors in ovarian carcinomas.

Gene therapeutic approaches currently favor adenoviral vectors over alternatively available vector systems. Ovarian cancer represents an attractive model for an intraperitoneal adenovirus-based gene therapy, which is now under intensive clinical investigation. Adenovirus-mediated gene transfer depends on adequate virus uptake and thus on the presence of sufficient amounts of high-affinity coxsackie-adenovirus receptor (CAR) and alphavbeta3- and alphavbeta5 integrins on target cells. This fact has been ignored in most ongoing clinical trials. This investigation, therefore, determined expression of CAR by immunohistochemistry in 37 ovarian carcinomas and compared it with that of alphavbeta3 and alphavbeta5 integrins. In all samples, except one undifferentiated carcinoma, CAR was immunohistochemically demonstrable. Grade 1 tumors exhibited stronger CAR immunostaining as compared with higher-grade cancers (P < 0.03). Integrins alphavbeta3 and alphavbeta5 were detectable in 62% and 65% of carcinomas, respectively, and staining for both classes correlated positively (P < 0.005). Cancers classified as undifferentiated completely lacked alphavbeta3 expression. Furthermore, in undifferentiated and grade 3 carcinomas the three molecules studied exhibited marked distributional heterogeneity with regard to focal positivity and negativity within the same tumor. Either the absence of CAR, alphavbeta3 and alphavbeta5 or the pronounced heterogeneity in their expression might seriously compromise the efficiency of adenovirus-based gene therapy in ovarian cancer.

Adenoviridae↗
PubMed2002

The development of an ELISA for chicken apolipoprotein II quantitation.

Polyclonal antibodies raised against chicken apoll was characterised for its use in Western blotting and ELISA detection systems of apoll in chicken plasma. The antibody has a high avidity and specificity for apolipoprotein II (apoII). Western blots show that the antibody reacts with a single band at 15 kDa. The antibody was used for setting up both direct and indirect ELISA assays for apoll. The indirect ELISA has a broader detection range (10-1,600U/mL) than the direct ELISA (10-100U/mL). It was found that both ELISA systems discriminate very well between vitellogenic (laying hen) and non-vitellogenic (rooster) plasma. The in- direct ELISA, due to its broad detection range, can potentially be used for monitoring female reproductive cycles, accidental and environmental exposure of males to estrogen, and for apoII secretion by cultured hepatocytes and hepatomas.

Animals↗
PubMed2002

Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells.

Chemotherapy does not have a prominent role in the treatment of hepatoma. However, an acyclic retinoid prevented tumor recurrence post-hepatectomy, and tamoxifen (TAM) induced apoptosis in tumor cells. Combination therapy of these agents on proliferation and apoptosis of hepatoma cells has not been explored. HepG2, Hep1B, Hepa1-6 and MH1C1 hepatoma cells were incubated with TAM, 9-cis- and all-trans retinoic acid (CRA, ATRA, respectively) alone or in combination. Proliferation rate was assessed and apoptosis was analyzed by flow cytometry, immunostaining, caspase activity assays and the expression of apoptosis- and/or cell cycle-related molecules. CRA and TAM, but not ATRA monotherapy were moderately effective. Apoptosis was accompanied by upregulation of caspase 3 and 8 activity, and increased p27, bax, caspase 3 expression, while the levels of p21cip/waf and bcl-2 were unchanged or decreased. Combination therapy enhanced apoptosis from a maximum of 60% after monotherapy to more than 90% after 96 h in all cell types. Pro-apoptotic effects were paralleled by inhibition of proliferation. Combination of TAM and CRA, but not ATRA, have an additive to synergistic anti-proliferative and pro-apoptotic effect on HCC cells. This justifies trials for HCC using combinations of these biological response modifiers.

Animals↗
PubMed2002

Intake of grapefruit juice alters the metabolic pattern of cyclosporin A in renal transplant recipients.

OBJECTIVE: The aim of the present study was to investigate the effect of grapefruit juice on the pharmacokinetics of cyclosporin A (CsA), as Sandimmun Neoral, and its main metabolites, M1, M9 and M4N, in renal transplant recipients. METHODS: Ten renal transplant recipients, on CsA-based immunosuppressive therapy, were included in this open, randomized crossover study. Patients were given their individualized morning dose of CsA, administered with either 250 ml water or 250 ml grapefruit juice and 12-hour CsA pharmacokinetic investigations were performed. The 2 investigation days were separated by at least 7 days. RESULTS: Administration of CsA with grapefruit juice compared with water significantly increased the area under the whole blood concentration versus time curve in the interval from 0-12 hours (AUC(0-12)) of CsA, by an average of 25 +/- 19% (p = 0.002). Intake of grapefruit juice did not have any significant influence on maximum whole blood concentration (Cmax) or time to Cmax (tmax) of CsA. AUC(0-12) and Cmax of M9 decreased significantly with intake of grapefruit juice, on average 22 +/- 11% (p = 0.0007) and 36 +/- 6% (p = 0.0001), respectively. AUC(0-12) of M1, however, was on average 13 +/- 14% (p = 0.02) higher upon co-administration of CsA with grapefruit juice as compared with water. The level of M4N was below the limit of quantification in most samples, and an effect of co-administration of CsA with grapefruit juice could not be determined for this metabolite. CONCLUSION: The present study shows that co-administration of grapefruit juice with CsA compared with water affects the formation and/or elimination of the 2 metabolites M1 and M9 differently. In addition, administration of CsA with grapefruit juice compared with water induced a moderate, but significant increase in systemic exposure of CsA in renal transplant recipients.

Adolescent↗
PubMed2001

A subpopulation of mitochondria prevents cytosolic calcium overload in endothelial cells after cold ischemia/reperfusion.

BACKGROUND: Calcium represents a key mediator of cold ischemia/reperfusion (CIR) injury presumably by affecting mitochondrial function. In this study, we investigated cellular and mitochondrial changes of calcium homeostasis in sublethally damaged human endothelial cells. METHODS: Changes in cellular and mitochondrial calcium concentrations were studied after cold ischemia in University of Wisconsin solution for 12 hr and reperfusion in ringer solution. Cytosolic-free calcium concentration ([Ca2+]c) and mitochondrial-free calcium content ([Ca2+]m) were analyzed by fura-2 and rhod-2 fluorescence, respectively. Pretreatment of cells with ruthenium red (RR) or a H+-ionophore was used to inhibit mitochondrial calcium uptake. Mitochondrial membrane potential (DeltaPsim) was measured by 5,5',6,6'-tetrachloro- 1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide and 3,3'-dihexyloxacarbocyanine iodide fluorescence. RESULTS: Twelve-hr cold ischemia did not induce apoptosis in endothelial cells. In such sublethally damaged cells, [Ca2+]c rose from approximately 20 nmol/L after cold ischemia to approximately 120 nmol/L during reperfusion. Pretreatment with RR leads to an approximately 5-fold rise in [Ca2+]c. Image analysis revealed a significant increase of [Ca2+]m in a subpopulation of mitochondria during reperfusion. This was not the case in RR-pretreated cells. DeltaPsim decreased significantly during cold ischemia and was sustained during reperfusion. The loss of DeltaPsim can be related to a reduced portion of mitochondria exhibiting high DeltaPsim. CONCLUSIONS: Our results suggest that cytosolic calcium influx during CIR is buffered by a selective portion of mitochondria in human umbilical vein endothelial cells. These mitochondria protect cells against cytosolic calcium overload and probably against subsequent cell injury.

Calcium↗
PubMed2001

p-Hydroxyphenylacetaldehyde, the major product of tyrosine oxidation by the activated myeloperoxidase system can act as an antioxidant in LDL.

The oxidative modification of low density lipoprotein (LDL) may play a significant role in atherogenesis. HOCl generated by the myeloperoxidase/H2O2/Cl- system of activated neutrophils may be operative in vivo making LDL atherogenic. Tyrosine has been found to be oxidized by HOCl to p-hydroxyphenylacetaldehyde (p-HA) capable of modifying phospholipid amino groups in LDL. As an amphiphatic phenolic compound, p-HA may have the potential to act as an antioxidant in the lipid phase of LDL. The present results show that (a) tyrosine exerts a protective effect on LDL modification by HOCl, (b) p-HA could act as antioxidant associated with the lipoprotein preventing cell- and transition metal ion-mediated LDL oxidation and (c) p-HA was able to scavenge free radicals.

Acetaldehyde↗
PubMed2001

Semicarbazide-sensitive amine oxidase catalyzes endothelial cell-mediated low density lipoprotein oxidation.

OBJECTIVE: Deamination products of semicarbazide-sensitive amine oxidases (SSAO), i.e. aldehydes, superoxide and ammonia have been shown to initiate vascular damage. SSAOs are copper-enzymes, present in endothelial (EC), smooth muscle cells (SMC) and in blood. Transition metals ions (Cu, Fe) mediate the oxidative (atherogenic) modification of LDL by SMC and EC. The physiological source of the active metal ions is still under debate. We hypothesize that SSAOs may catalyze LDL oxidation by endothelial cells via enzyme-complexed Cu++. METHODS: EC isolated from human umbilical veins and cultured in 35 mm wells in RPMI-1640 medium were used as LDL oxidation system. RESULTS: Diamine oxidase (DAO), a SSAO which activity is elevated in tissues and sera of diabetic patients, catalyzes the oxidation of LDL by EC. In the presence of purified DAO (0.07 to 70 U/l) LDL oxidation was increased up to 10-fold as measured by thiobarbituric acid reactive substance (TBARS) formation as well as apoprotein modification of LDL. Chemical blockage of the SSAO substrate binding site did not inhibit the catalytic effect of DAO on LDL oxidation. Denaturation of the enzyme did not destroy the ability of the preparation to facilitate LDL oxidation by EC. The potential of the enzyme to catalyze LDL oxidation was not suppressed in the presence of serum. However, selective removing of enzyme-copper completely abolished the ability of the enzyme to trigger cell-mediated LDL oxidation. CONCLUSION: DAO, beside generating angiopathic deamination products, has the potential to act as a pathophysiological catalyst of LDL atherogenic modification by vascular cells.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Excessive infant crying: often not confined to the first 3 months of age.

Excessive crying/fussing in infancy may account for serious problems in mother-infant interactions but is believed to be self-limiting around the age of 3 months. A random digit dialling telephone survey weighted by sex, age, and population density and yielding 662 children aged 9 to <36 months was used to estimate prevalence and the proportion of cases where this problem extends beyond the third month postpartum. Excessive infant crying/fussing during the first 3 months of age was found in 21.0% (95% CI 17.9-24.1) and persisted for longer in 39.6% (95% CI 31.5-47.7) of these. Professionals consulting parents on crying problems should take into account its possible persistence for longer periods of time.

Adolescent↗
PubMed2001

Hormonal changes in aging men: a therapeutic indication?

The rise in male life expectancy is paralleled by increased age-related clinical signs and symptoms such as muscle weakness, osteoporosis, benign prostatic hyperplasia, changes in body composition, fatigue, decreased sexual interest and activity, and increased prevalence of erectile dysfunction, all of which limit the quality of life. Many of these symptoms are similar to those of clinically well-defined hormone deficiencies, e.g. Kallman syndrome, Prader--Labhart--Willi syndrome or deficiencies due to treatment of pituitary tumors. Three male endocrine axes are characterized by age-related changes in concentrations of circulating hormones: (i) the hypothalamic--pituitary--testicular axis with lower serum levels of testosterone (T) and higher serum levels of luteinizing and follicle-stimulating hormone, (ii) the hypothalamic--pituitary--adrenal axis with its gradual decline in dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), (iii) the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis showing decreased hormone production concomitant with symptoms similar to those of GH-deficient adults. The beneficial effects of hormone replacement in nonelderly hormone-deficient individuals and in postmenopausal women raised hope that hormone substitution might prevent or even reverse some of the symptoms of male aging. However, this approach is hampered by the lack of individual age-related hormone reference values and reliable clinical read-out parameters. The findings so far do not support the need for widespread hormone replacement in elderly men. Larger long-term prospective studies are needed to identify clinically useful read-out parameters, and then demonstrate that hormone replacement can translate into functional parameters, thereby providing the individual benefit of treatment for aging men.

Aging↗
PubMed2001

Is obesity a risk factor for childhood asthma?

BACKGROUND: In adolescents and adults, an association between obesity and asthma was found in females. Does this sex-specific association already exist in young children? METHODS: Questionnaire data on 9357 5- and 6-year-old German children were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma, hay fever, and eczema was ascertained with the ISAAC core and other validated questions. Overweight was defined by a BMI of >90th and < or =97th percentile and obesity by a BMI of >97th percentile. RESULTS: The lifetime prevalence of doctor's diagnosed asthma in girls was 3.5% (95%, CI 2.9-4.1%) for normal weight, 5.8% (95% CI 3.2-8.4%) for overweight, and 10.3% (95% CI 5.3-15.2%) for obesity, whereas no relation to weight was found in boys. Hay fever and eczema were unrelated to weight in girls and boys. The adjusted odds ratio for asthma in girls was 2.12 (95% CI 1.22-3.68) for overweight and 2.33 (95% CI 1.13-4.82) for obesity. CONCLUSIONS: A sex-specific association with doctor's diagnosed asthma was also observed in girls at school entry. Since this association was confined to doctor's diagnosed asthma in the absence of other atopic conditions, and no association with other atopic manifestations was found, we hypothesize that this association is related to factors other than atopic sensitization.

Asthma↗
PubMed2001

Stable genetic transformation of tomato plastids and expression of a foreign protein in fruit.

Transgenic chloroplasts offer unique advantages in plant biotechnology, including high-level foreign protein expression, absence of epigenetic effects, and gene containment due to the lack of transgene transmission through pollen. However, broad application of plastid genome engineering in biotechnology has been largely hampered by both the lack of chloroplast transformation systems for major crop plants and the usually low plastid gene expression levels in nongreen tissues such as fruits, tubers, and other storage organs. Here we describe the development of a plastid transformation system for tomato, Lycopersicon esculentum. This is the first report on the generation of fertile transplastomic plants in a food crop with an edible fruit. We show that chromoplasts in the tomato fruit express the transgene to approximately 50% of the expression levels in leaf chloroplasts. Given the generally very high foreign protein accumulation rates that can be achieved in transgenic chloroplasts (>40% of the total soluble protein), this system paves the way to efficient production of edible vaccines, pharmaceuticals, and antibodies in tomato.

Biotechnology↗
PubMed2001

Inheritance of tristyly in Oxalis tuberosa (Oxalidaceae).

Frequencies of floral morphs in progenies obtained from a complete set of diallelic crosses among three accessions of tristylous, octoploid oca (Oxalis tuberosa) were used for a Mendelian analysis of floral morph inheritance. The frequencies observed had the best fit to a model of tetrasomic inheritance with two diallelic factors, S, s and M, m, with S being epistatic over M. No explanation could be found for the unexpected formation of a small percentage of short-styled individuals in crosses between the mid-styled and the long-styled parent. For the acceptance of models of disomic and octosomic inheritance several additional assumptions would have to be made and therefore these modes of inheritance are less likely. Dosage-dependent inheritance of floral morph was rejected. Only a small frequency (36%) of the cross progenies flowered, in contrast to the greater propensity for flowering of O. tuberosa accessions held at gene banks.

Alleles↗
PubMed2001

Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Cells, Cultured↗
PubMed2001

Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines.

BACKGROUND: Since 1996 in Germany primary infant immunization against Haemophilus influenzae has been most commonly given in the form of diphtheria-tetanus toxoids-acellular pertussis/H. influenzae type b (DTaP/Hib) or diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b (DTaP-IPV/Hib) combination vaccines. These combination vaccines elicit lower anti-Hib antibody concentrations than the equivalent Hib conjugate administered as a separate injection, but the clinical relevance of this phenomenon is unknown. METHODS AND FINDINGS: To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent surveillance systems, one hospital- and one laboratory-based, were used during 1998 and 1999 for detection of cases. Vaccination histories of all cases detected were obtained by telephone contact with parents or health care providers. During the 2-year study period invasive H. influenzae disease in the <5-year age group continued to fall, with a mean annual incidence of 1.01/100 000 children. National vaccination coverage rates revealed that only 70% of children given DTaP/Hib or DTaP-IPV/Hib received the recommended three doses in their first year of life, but the overall effectiveness of these vaccines was high at 97.5% (95% confidence interval, 96.3 to 98.4) for those who had received at least one dose. In subjects who received the full 3-dose schedule, effectiveness was 98.8% (95% confidence interval, 98.2 to 99.3). CONCLUSION: Although it is well-documented that DTaP/Hib vaccines elicit lower anti-Hib titers than separate vaccines, such combinations are effective in reducing the incidence of invasive H. influenzae type b disease.

Antibodies, Bacterial↗
PubMed2001

Quartz exposure of the rat lung leads to a linear dose response in inflammation but not in oxidative DNA damage and mutagenicity.

Exposure to quartz and high concentrations of other poorly soluble particles can lead to the development of lung tumors in the rat. The mechanisms involved in particle-induced carcinogenesis seem to include inflammation-associated production of reactive oxygen species (ROS) and DNA damage. ROS induce 8-oxoguanine (8-oxoGua) and a panel of other oxidation products in DNA. In proliferating cells such DNA lesions can lead to various types of mutations, which might be critical for cancer-related genes with respect to tumor formation. Quartz is known to mediate the induction of 8-oxoGua in the nuclear DNA of lung cells when applied to the lung of rats. We have investigated the time- and dose-dependent biologic effects of quartz and, as a control, corundum, on cell proliferation and various pulmonary inflammation and toxicity markers in rat bronchoalveolar lavage fluid (BALF); on the induction of 8-oxoGua in the DNA of rat lung cells; and on the cellular levels of p53 wild-type and p53 mutant (mut) protein. Rats were exposed by intratracheal instillation to various amounts of quartz (0.3, 1.5, or 7.5 mg/rat) or corundum (0.3, 1.5, or 7.5 mg/rat) and measured at Days 7, 21, and 90 after exposure. Corundum had no adverse effects except a slight elevation of 8-oxoGua at a dose of 7.5 mg/rat. However, significant changes in the BALF were detected at all quartz doses. 8-oxoGua was significantly increased only at 1.5 and 7.5 mg quartz/rat. The amount of cells with detectable p53 wild-type protein levels was increased at 1.5 and 7.5 mg quartz/rat at 7 and 21 d. Elevated amounts of cells with enhanced p53 mut protein levels were measured at all time points after instillation of 7.5 mg quartz/rat.

Aluminum Oxide↗
PubMed2001

Magnetic resonance volumetric study of the temporal lobe structures in ischaemic vascular dementia.

Dementia of Alzheimer type and vascular dementias account for as much as 90% of all dementias. MRI volumetry of the temporal lobe is often performed in Alzheimer's disease, but there are only a few studies that evaluate temporal lobe atrophy in vascular dementia. We therefore compared volumes of the superior temporal gyrus (STG), basolateral temporal area (BTG--the region including middle temporal gyrus, inferior temporal gyrus and fusiform gyrus), parahippocampal gyrus (PAH), head of the hippocampus (HIP), amygdaloid body (AA) and temporal horn of the lateral ventricle (LV) separately for each hemisphere in 8 patients with ischaemic vascular dementia (IVD) and in 14 cognitively and neurologically normal subjects. In the left hemisphere basolateral temporal area, parahippocampal gyrus, amygdaloid body and hippocampal head had significantly smaller volumes in IVD patients than in age-matched control group. In the right hemisphere the significant atrophy in IVD patients concerned only basolateral temporal area.

Aged↗
PubMed2000

New insights into p53 regulation and gene therapy for cancer.

Due to its critical involvement in cell cycle control and apoptotic signaling, the transcription factor p53 has become the most important tumor suppressor currently under investigation. TP53 is the most frequently mutated gene in human cancers and is thought to play a crucial role in malignant transformation. Therefore, p53 appears to be an appealing target for gene therapy. Adenoviral-based p53 gene transfection is now being introduced in large clinical trials. Viral cell entry was found to be the rate-limiting step of gene delivery and thus of therapeutic efficiency. Attachment of adenoviruses to the target cell surface is mediated through the coxsackie-adenovirus receptor, and internalization is achieved via interactions with integrins of the alpha v beta(3) and alpha v beta(5) class. The assumption that the restitution of the p53-dependent apoptotic pathway results in a higher responsiveness of solid tumors to cytostatic agents remains a major matter of debate. Combinations of p53-based gene therapy with other components involved in apoptosis, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/APO2L, or agents neutralizing tumor-promoting antiapoptotic signals, such as humanized anti-growth factor antibodies, should further improve the effectiveness of cancer treatment in the future.

Drug Resistance, Neoplasm↗