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Biomedical subjects

M Hofmann

Publications and source records attributed to M Hofmann.

At least 109 records · Page 6Linked to original sources
PubMed1998

Oxygen radical generation and enzymatic properties of mitochondria in hypoxia/reoxygenation.

The time-dependence of oxygen radical formation and development of enzymatic dysfunction after hypoxia/reoxygenation was investigated in isolated rat liver mitochondria. Generation of oxygen radicals was studied by electron paramagnetic resonance (EPR) spectroscopy using the spin trap DMPO (5,5-dimethyl-l-pyrroline-N-oxide). The spin adduct DMPO-OH was found to be formed from the primarily generated adduct of DMPO with the superoxide anion radical (DMPO-OOH). Hypoxic storage followed by reoxygenation at room temperature resulted in an increased decay rate of the DMPO-OH spin adduct while its steady state concentration remained unchanged. This finding strongly suggests an increased rate of DMPO-OH formation which originally derived from enhanced superoxide anion radical production due to hypoxia/reoxygenation. The enhanced superoxide radical formation seems to be due to dysfunction of respiratory chain enzymes, resulting in increased levels of reductive components. In agreement with that, we found the decrease of respiration control and ATP synthesis activity at a similar time scale as that for DMPO-OH adduct formation. The increase of superoxide radical formation and of the reductive capacity of mitochondria was accompanied by a decrease in membrane order at the polar interface. Oxidative phosphorylation was completely abolished after 30 min of hypoxic storage, whereas ATP synthesis decreased significantly after 15 min of hypoxia.

Adenosine Triphosphate↗
PubMed1998

[Classical swine fever in 1993 in Switzerland: molecular-epidemiologic characterization of the virus isolate].

RT-PCR followed by direct nucleotide sequencing of the amplified cDNA was carried out to analyse most of the 5' nontranslated region (5'NTR) of classical swine fever virus (CSFV) isolates from the five 1993 disease outbreaks in Switzerland. Sequence data were compared to other CSFV strains, and dendrograms were constructed in order to determine the phylogenetic relationship of the Swiss virus strains. Dendrograms formed by the analysis of different parts of the 5'NTR were compared. It was shown that all Swiss isolates were related to other CSFV strains involved in disease outbreaks in Europe in the 1990s. Two of the isolates were indistinguishable from a CSFV strain isolated from wild boar meat imported from China into Austria in 1993. The risk of introducing classical swine fever by improperly treated swill and, in particular by importing wild boar meat is discussed.

Animals↗
PubMed1997

A high throughput screening for rarely transcribed differentially expressed genes.

A novel method combining elements of suppression subtractive hybridization with high throughput differential screening permits the efficient and rapid cloning of rarely transcribed differentially expressed genes. The experimental strategy virtually excludes the possibility of isolating false positive clones. The potential of the method is demonstrated by the isolation of 625 differentially expressed cDNAs from the metastatic adenocarcinoma cell line Bsp73-ASML when subtracted from its non-metastatic counterpart Bsp73-1AS. Northern analysis of 72 randomly selected clones demonstrated that 68 were differentially expressed with respect to Bsp73-ASML, indicating a true positive rate of 94%. Additionally, a large proportion of these clones represented rare transcripts as determined by the exposure time required to detect a signal. Sequence data indicated that of the 625 clones obtained, 92 clones scored perfect or near perfect matches with already known genes. Two hundred and eighty one clones scored between 60 and 95% homology to known human and mouse genes, whereas 252 clones scored no match with any sequences in the public databases. The method we describe is ideally suited whenever subtle changes in gene expression profiles need to be determined.

Adenocarcinoma↗
PubMed1997

Randomized comparison of angioplasty of complex coronary lesions at a single center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Study.

BACKGROUND: The purpose of this study was to test whether coronary revascularization with ablation of either excimer laser or rotational atherectomy can improve the initial angiographic and clinical outcomes compared with dilatation (balloon angioplasty) alone. METHODS AND RESULTS: At a single center, a total of 685 patients with symptomatic coronary disease warranting elective percutaneous revascularization for a complex lesion were randomly assigned to balloon angioplasty (n = 222), excimer laser angioplasty (n = 232), or rotational atherectomy (n = 231). The primary end point was procedural success (diameter stenosis < 50%, absence of death, Q-wave myocardial infarction, or coronary artery bypass surgery). The patients who underwent rotational atherectomy had a higher rate of procedural success than those who underwent excimer laser angioplasty or conventional balloon angioplasty (89% versus 77% and 80%, P = .0019), but no difference was observed in major in-hospital complications (3.2% versus 4.3% versus 3.1%, P = .71). At the 6-month follow-up, revascularization of the original target lesion was performed more frequently in the rotational atherectomy group (42.4%) and the excimer laser group (46.0%) than in the angioplasty group (31.9%, P = .013). CONCLUSIONS: Procedural success of rotational atherectomy is superior to laser angioplasty and balloon angioplasty; however, it does not result in better late outcomes. The role of plaque debulking before balloon dilatation in percutaneous coronary revascularization remains to be fully defined.

Adult↗
PubMed1997

An essential role for CD44 variant isoforms in epidermal Langerhans cell and blood dendritic cell function.

Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC) leave peripheral organs and home to lymph nodes via the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors to lymph nodes, we explored the expression of CD44 proteins on migrating LC and DC. We show that upon antigen contact, LC and DC upregulate pan CD44 epitopes and epitopes encoded by variant exons v4, v5, v6, and v9. Antibodies against CD44 epitopes inhibit the emigration of LC from the epidermis, prevent binding of activated LC and DC to the T cell zones of lymph nodes, and severely inhibit their capacity to induce a delayed type hypersensitivity reaction to a skin hapten in vivo. Our results demonstrate that CD44 splice variant expression is obligatory for the migration and function of LC and DC.

Animals↗
PubMed1997

Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)--correlation with simultaneous rCBF-PET measurements.

We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (-4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29 and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the left superior partietal cortex and on the left prefrontal cortex simultaneous increases in [HbO2] as well as [HbT] in both cortical regions in the healthy elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2] and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.

Aged↗
PubMed1997

[The Wolfram syndrome: diabetes mellitus, hypacusis, optic atrophy and short stature in STH deficiency].

HISTORY AND CLINICAL FINDINGS: A 43-year-old man was known for 3 years to have diabetes mellitus. For 2 months before admission he had symptoms of hyperglycaemia with polyuria, polydipsia, weight loss, as well as impairment of vision and declining fitness. In addition to bilateral deafness he was clearly of normally proportioned short stature (150 cm). INVESTIGATIONS: The levels of blood sugar (221 mg/dl), HbA1c(10.2%), triglycerides (496 mg/dl) and cholesterol (323 mg/dl) were raised, while the concentration of somatotropic hormone was diminished, both before and after arginine administration. Fundoscopy revealed concentric diminution of the visual fields with left amblyopia. Visual evoked potentials and colour sense testing revealed bilateral optical atrophy, and the audiogram demonstrated deafness. These findings provided the diagnosis of Wolfram syndrome, namely insulin-dependent diabetes mellitus, deafness, optical atrophy and small stature with somatotropic hormone deficiency. TREATMENT AND COURSE: On insulin treatment the metabolic state became normal (HbA1c 7.5%, normal lipid profile). It was decided that the deficiency in somatotropic hormone regulation did not require treatment. CONCLUSION: Cardinal symptoms of the autosomally recessive Wolfram syndrome are insulin-dependent diabetes and optic nerve atrophy. Several types of hormonal abnormalities are associated with it, including a deficiency in the somatotropic axis. To obtain early and adequate hormonal substitution requires extensive endocrinological diagnosis of a disease which frequently becomes manifest in childhood or adolescence.

Adult↗
PubMed1997

[D-dimer, thrombin-antithrombin III-complex (TAT) and prothrombin fragment 1+2 (PTF). Parameters for monitoring therapy with low molecular-weight heparin in coagulation disorders].

Two groups of 15 patients each with disseminated intravascular coagulation in association with septic disease were treated with low-molecular-weight heparin (lmw-heparin) in different dosages (group I: 1.5-5 IE/kg body weight (BW) per hour; group II: 8-15 IE/kg BW). We studied the levels of D-dimer, thrombin-antithrombin III complex (TAT), prothrombin fragments 1 and 2 (PTF), and global tests of coagulation like prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT) and platelet count, plasminogen activation (PA) and fibrinogen concentration to estimate the success of heparin therapy in the two groups. TT and fibrinogen concentration were not suitable to follow the course of the coagulation disorder, PT, PTT, platelet count progressively PA, D-dimer, TAT, and PTF normalised progressively after heparinisation. However, only the last three parameters were sensitive enough to show different effects of variable dosages of lmw-heparin. D-dimer, TAT, and PTF levels declined in proportion with heparin concentrations, and thus appear to be the most useful parameters for monitoring the therapeutic effect of heparin in septic coagulopathies.

Anticoagulants↗
PubMed1997

Characterization of mouse and human nude genes.

The differentiation of primitive epithelial precursor cells in the thymic primordium into subcapsular, cortical, and medullary epithelial cells of the mature thymus requires the activity of the nude gene product Whn. Whn is also required for proper keratinization of the hair shaft. We determined the nucleotide sequence of a 58 kilobase region on mouse chromosome 11 that encompasses the mouse nude gene and part of the two neighboring genes, encoding a sodium/dicarboxylate co-transporter and the retinal protein 4. Using cross-hybridization, the human orthologue of the mouse nude gene was isolated. The human WHN protein also consists of 648 amino acids, 85% of which are identical to the mouse protein. Like the mouse gene, the human gene consists of eight coding exons and utilizes two alternative first exons in a tissue-specific fashion. Sequences upstream of the two alternative first exons display promoter activity in heterologous reporter assays. Whereas both promoters appear to be active in skin (albeit at different levels), only the most upstream element is active in the thymus, indicating that transcriptional activity of the whn gene is subject to complex regulation. Nucleotide sequence database comparisons reveal that among other winged-helix genes, the HTLF and HTLFL1 genes are most closely related to whn, although the exon/intron structure of the human HTLF gene in the DNA binding domain differs from that of whn.

Alternative Splicing↗
PubMed1997

750 MHz HPLC-NMR spectroscopic identification of rat microsomal metabolites of phenoxypyridines.

Directly coupled 750 MHz HPLC-1H NMR spectroscopy has been applied to the characterisation of low level metabolites of 3-amino-2-(2-fluorophenoxy)pyridine (AP) and 3-nitro-2-(2-fluorophenoxy)pyridine (NP) in rat microsomes. In stop-flow HPLC-NMR mode, the direct injection of microsomal extracts enabled the separation and characterisation of minor metabolites. NP is converted into AP to an extent of 93.4% and this is further metabolised to 4- and 6-hydroxy-AP (6 and 0.6% respectively). Unequivocal identification of these metabolites was achieved without the use of a radiolabel or synthetic standards and thus demonstrates the applicability of directly coupled HPLC-NMR to metabolite identification in in vitro systems. The potential exists for HPLC-NMR and HPLC-NMR-MS to provide rapid metabolic information within the timescale of high throughput lead optimisation exercises in drug discovery.

Animals↗
PubMed1997

Tissue factor antigen is elevated in patients with microvascular complications of diabetes mellitus.

Patients with late diabetic complications have increased levels of parameters indicating activation of coagulation (Takakashi et al., 1989; Ceriello, 1993; Murakami et al., 1993; Kario et al., 1995; Shimizu et al., 1995; Yokoyama et al., 1996), endothelial cell damage (Jensen, 1989; Iwashima et al., 1990; Sernau et al., 1995; Gabath et al., 1996). TF is believed to activate the coagulation mechanism in patients with late complications of diabetes. We studied the TF antigen plasma levels in 72 patients with diabetes mellitus (36 type I, 36 type II) with respect to its relevance as a marker of microvascular diabetic complications. TF levels did not correlate with macrovascular disease, diabetes type or age. Sixty patients with decreased renal function not due to diabetes were studied for evaluation of the contribution of renal failure to TF antigen plasma levels. We did not find a significant correlation of TF with s-creatinine in non diabetic patients (r = 0.27, p > 0.05). However, TF levels were elevated in diabetic patients with microvascular disease. Patients with retinopathy had higher TF levels than without (0.30 ng/ml vs 0.11 ng/ml, p < 0.007). When patients were divided into subgroups according to the urine albumin concentration, TF antigen of patients without albuminuria (0.019 ng/ml, n = 25) did not differ from patients with microalbuminuria (0.095 ng/ml, n = 19 p > 0.05). However, TF levels were significantly higher in patients with macroalbuminuria (n = 28; 0.215 ng/ml, p < 0.005). Thus activation of coagulation in patients with microvascular complications of diabetes may be triggered by tissue factor.

Adult↗
PubMed1997

The antioxidant properties of thioctic acid: characterization by cyclic voltammetry.

Thioctic acid (TA) level and its antioxidant capacity were monitored by cyclic voltammetry (CV), in solution and in human plasma. A linear correlation between the anodic wave current Ia at 900 mV and [TA] was obtained. This indicates that TA, commonly found in human plasma, is an antioxidant component characterized by a potential E1/2 = 900 mV and constitute, at least in part, the second anodic wave of the CV tracing. When plasma from diabetic patients was analyzed by CV, those patients under treatment with TA showed higher Ia than others not taking the drug. When the patients under treatment with TA were divided into groups according to the severity of their nephropathy, or according to the severity of their total complication count, Ia levels representing TA were significantly higher in those patients with more severe complications.

Adult↗
PubMed1997

Identification of peripheral vascular disease in elderly subjects using optical spectroscopy.

The purpose of this study was to determine the usefulness of near-infrared spectroscopy (NIRS) measurements to identify peripheral vascular disease (PVD). Usefulness was determined by the frequency of a successful test, as well as comparison with standard clinical assessments. Study subjects (N = 117, mean age = 67.8 +/- 8.1 yrs) responded to a free screening for PVD. NIRS was used to measure the relative O2 saturation of hemoglobin in the soleus muscle. The time to 1/2 recovery of O2 saturation (O2T1/2) was measured after 1 minute of repeated plantar flexions using a Cybex Eagle seated calf machine. O2T1/2 was used as many subjects had recovery curves that did not have an exponential line shape. The test was done on both legs and the worst leg was used for analysis. For comparative purposes, a clinical history and physical examination were performed by a physician or nurse practitioner, which included questions on intermittent claudication, examination of peripheral pulses, and questions to identify cardiovascular risk factors. NIRS signals were obtained on 105 of 117 subjects (89% success rate). Subjects with body mass index (BMI) values above 32 appeared to have NIRS O2T1/2 values that were less reliable than subjects with BMI values < or = 32 (77% success rate). The O2T1/2 was longer in subjects with claudication and reduced pulses than in subjects without these conditions. Sensitivity comparing O2T1/2 to claudication and reduced pulse varied from 51-76% and specificity from 65-80%, depending on the cutoff value for O2T1/2 that was used (normal value plus 1 or 2 SD). A longer O2T1/2 was significantly associated with incidence of diabetes, smoking, hypercholesterol, and coronary bypass surgery. In summary, successful NIRS O2T1/2 measurements were made in 77% of the subjects, with failure primarily occurring in obese subjects. NIRS O2T1/2 measurements showed reasonable although not strong agreements with clinical assessment of PVD, and with some risk factors for cardiovascular disease.

Aged↗
PubMed1997

Endotracheal placement of balloon-expanded stents: an experimental study in rabbits.

The authors implanted balloon-expanded stents in the trachea of 10 rabbits for 1 day to 6 months. Follow-up included chest radiography, clinical examination, light microscopy, and scanning electron microscopy. Pneumothorax occurred in two cases after placement, marked stridor due to mucus plugging in all cases, signs of infection in three cases (two of which developed into pneumonitis), compression of the upper stent end in two cases, and moderate to severe mucus plugging in all cases. Microscopically, none of the stents was completely covered with epithelium even at 6 months. The high rate of complications may be a result of the rigid construction, which does not allow tracheal movement or adaptation of the stent shape to the shape of the trachea.

Animals↗
PubMed1997

Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells.

Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs) with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative stress led to the activation of the transcription factor NF-kappaB and thus promoted the upregulation of various NF-kappaB-controlled genes, including endothelial tissue factor. Supplementation of the cellular antioxidative defense with the natural occurring antioxidant alpha-lipoic acid before AGE albumin induction completely prevented the AGE albumin-dependent depletion of reduced glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs) revealed that AGE albumin-mediated NF-kappaB activation was also reduced in a time- and dose-dependent manner as long as alpha-lipoic acid was added at least 30 min before AGE albumin stimulation. Inhibition was not due to physical interactions with protein DNA binding, since alpha-lipoic acid, directly included into the binding reaction, did not prevent binding activity of recombinant NF-kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the release and translocation of NF-kappaB from the cytoplasm into the nucleus. As a consequence, alpha-lipoic acid reduced AGE albumin-induced NF-kappaB mediated transcription and expression of endothelial genes relevant in diabetes, such as tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro.

Antioxidants↗