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J Hoffmann

Publications and source records attributed to J Hoffmann.

At least 91 records · Page 5Linked to original sources
PubMed2000

Cloning and analysis of a cecropin gene from the malaria vector mosquito, Anopheles gambiae.

Parasites of the genus Plasmodium are transmitted to mammalian hosts by anopheline mosquitoes. Within the insect vector, parasite growth and development are potentially limited by antimicrobial defence molecules. Here, we describe the isolation of cDNA and genomic clones encoding a cecropin antibacterial peptide from the malaria vector mosquito Anopheles gambiae. The locus was mapped to polytene division 1C of the X chromosome. Cecropin RNA was induced by infection with bacteria and Plasmodium. RNA levels varied in different body parts of the adult mosquito. During development, cecropin expression was limited to the early pupal stage. The peptide was purified from both adult mosquitoes and cell culture supernatants. Anopheles gambiae synthetic cecropins displayed activity against Gram-negative and Gram-positive bacteria, filamentous fungi and yeasts.

Amino Acid Sequence↗
PubMed2000

Safety and preliminary efficacy of one month glycoprotein IIb/IIIa inhibition with lefradafiban in patients with acute coronary syndromes without ST-elevation; a phase II study.

AIMS: Oral glycoprotein IIb/IIIa inhibitors might enhance the early benefit of an intravenous agent and prevent subsequent cardiac events in patients with acute coronary syndromes. We assessed the safety and preliminary efficacy of 1 month treatment with three dose levels of the oral GP IIb/IIIa blocker lefradafiban in patients with unstable angina or myocardial infarction without persistent ST elevation. METHODS: The Fibrinogen Receptor Occupancy STudy (FROST) was designed as a dose-escalation trial with 20, 30 and 45 mg lefradafiban t.i.d. or placebo. Five hundred and thirty-one patients were randomized in a 3:1 ratio to lefradafiban or placebo in a double-blind manner. Efficacy was assessed by the incidence of death, myocardial infarction, coronary revascularization and recurrent angina. Safety was evaluated by the occurrence of bleeding classified according to the TIMI criteria and by measuring clinical laboratory parameters. RESULTS: There was a trend towards a reduction in cardiac events with lefradafiban 30 mg when compared with placebo and lefradafiban 20 mg. The benefit was particularly apparent in patients with a positive (> or = O.1 ng. ml(-1)) troponin I test at baseline and less so in those with a negative test result. In patients receiving lefradafiban, the cardiac event rate decreased with increasing minimal levels of fibrinogen receptor occupancy. There was a dose-dependent increase in the incidence of bleeding: the composite of major or minor bleeding occurred in 1% of placebo patients, 5% of patients receiving lefradafiban 20 mg and in 7% of patients receiving 30 mg, with an excessive risk (15%) in the 45 mg group which resulted in early discontinuation of this dose level. Gingival and arterial or venous puncture site bleedings were most common and accounted for more than 60% of all haemorrhagic events. There was an increased incidence of neutropenia (neutrophils <1. 5 x 10(9)/l) in the lefradafiban groups (5.2% vs 1.5% in the placebo group), which did not result from bone marrow depression but rather from a reversible redistribution of neutrophils by margination or clustering. CONCLUSION: One month's treatment with the oral glycoprotein IIb/IIIa inhibitor lefradafiban in patients with unstable angina and myocardial infarction without persistent ST elevation resulted in a decrease in cardiac events with lefradafiban 30 mg and a dose-dependent increase in haemorrhagic events. The observed favourable trend towards a reduction in cardiac events in patients with elevated troponin levels requires confirmation in a large clinical trial.

Aged↗
PubMed2000

Antioxidant status of surgical patients receiving TPN with an omega-3-fatty acid-containing lipid emulsion supplemented with alpha-tocopherol.

BACKGROUND: LCT lipid emulsions and even more fish oil-containing lipid emulsions are under debate regarding their tocopherol and PUFA content as well as their effect on the antioxidative status especially in patients with oxidative stress. METHODS: Thirty-three patients undergoing major abdominal surgery were randomly assigned to receive either an alpha-tocopherol-supplemented (562 micromol/l) MCT/LCT/omega-3-acid triglycerides (MLF, 5/4/1 w/w/w, 20%) emulsion or a soybean oil-based LCT emulsion (20%). The TPN regimen continuously provided 1.4 g fat kg bw(-1)d(-1)over 5 days. RESULTS: Plasma antioxidant concentrations were strongly reduced by surgical treatment. Following 5 days of TPN with the MLF emulsion, mean plasma alpha-tocopherol increased by 20.0 micromol/l (1.98 micromol/mmol lipid), while nearly no change was observed in the LCT emulsion group. In both groups, plasma concentrations of all non-supplemented antioxidants (vitamin C, carotenoids, selenium) as well as serum total antioxidant capacity further decreased during TPN. The concentrations of plasma cholesterol oxidation products as a measure of in vivo lipid peroxidation revealed no changes over the TPN period in either group. CONCLUSION: In contrast to the LCT emulsion, administration of the a-tocopherol supplemented MLF lipid emulsion normalized a-tocopherol plasma concentrations. Despite its high long-chain PUFA content, no hint for increased lipid peroxidation was found.

Abdomen↗
PubMed2000

Arrhythmia risk stratification in idiopathic dilated cardiomyopathy based on echocardiography and 12-lead, signal-averaged, and 24-hour holter electrocardiography.

BACKGROUND: To date, considerable controversy exists regarding noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC). Methods and Results Between 1992 and 1997, 202 patients with IDC without a history of sustained ventricular tachycardia (VT) underwent echocardiography, signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major arrhythmic events, including sustained VT, ventricular fibrillation, or sudden death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and nonsustained VT on Holter as the only independent arrhythmia risk predictors. The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was associated with a 14. 3-fold risk for future arrhythmic events (95% confidence interval 2. 3-90). To further elucidate the prognostic value of LV ejection fraction, multivariate Cox analysis was repeated with ejection fraction forced to remain in the model. In the latter model, an ejection fraction </=30% combined with nonsustained VT on Holter was found to be a significant arrhythmia risk predictor with a relative risk of 14.6 (95% confidence interval 2.2-97). CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT on Holter, and the combination of LV ejection fraction </=30% and nonsustained VT on Holter, identify a subgroup of patients with IDC with a 14-fold risk for subsequent arrhythmic events. These findings have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in patients with IDC.

Adolescent↗
PubMed2000

A possible role for the Alzheimer amyloid precursor protein in the regulation of epidermal basal cell proliferation.

The regulation of epidermal growth involves a number of ions, growth factors and cytokines and possibly additional but as yet unknown factors. Here we report on the potential role of the secretory N-terminal domain (sAPP) of the Alzheimer amyloid precursor protein (APP) in the regulation of keratinocyte proliferation. In human skin APP was detectable predominantly in the basal cell layer of the epidermis whereas the immunocytochemical signal in the underlying mesenchymal tissue was very low. Cultured normal human keratinocytes expressed the three APP isoforms 695, 751 and 770 with highest values for the isoforms 751 and 770. HaCaT cells, a spontaneously immortalized human keratinocyte cell line, exhibited almost identical patterns in the expression of the APP isoforms and in the release of endogenous sAPP. In HaCaT cells, recombinant sAPP (sAPPrec) was found to compete with endogenous sAPP for the same binding sites. Binding of sAPPrec was specific and occurred in microdomains of approximately 0.1 to approximately 0.3 microm in diameter. At 10 nM, sAPPrec binding induced a 2- to 4-fold increase in the rate of cell growth. sAPP concentrations in the conditioned media were found to reach 5-20 nM which is in the mitogenic range of sAPPrec. The proliferative effect of sAPP was inhibited by approximately 50% when antisense oligonucleotides directed against the APP mRNA were applied. The predominant expression of

Alzheimer Disease↗
PubMed2000

Global-local orientation congruency effects in visual search.

In a visual search task, subjects had to decide which of 2 possible target letters was presented among 12 distractor letters. The 13 characters were arranged to form a global Navon-type letter. The global letter and the local letters (target and distractors) were independently presented in four different viewer-related orientations. When the global letter and the target were frequently congruently oriented, the response times increased with growing orientation disparity between them. This global-target congruency effect was independent from target identity (Experiment 1), and it diminished when global and target orientations were not correlated (Experiment 2). The results indicate that the orientation of the global letter can be deliberately used in order to facilitate the processing of congruently oriented local targets. The alignment of a spatial frame of reference is discussed as the most probable process underlying this facilitation.

Adult↗
PubMed2000

Linear lesion formation by ND:YAG laser versus radiofrequency energy in porcine atria.

The efficacy of RF energy versus the neodymium:yittrium aluminum-garnet laser to create linear lesions was compared in fresh ex vivo swine hearts. A total of 598 lesions were created in four locations: ostium of the pulmonary veins, trabeculated lateral left atrium, smooth posterior part of the right atrium, and the isthmus between the inferior vena cava and tricuspid valve. A 400-micron bare quartz fiber with CO2 cooling (distance to the tissue 5, 10, and 15 mm) and an RF ablation catheter (4-mm tip) were mechanically dragged over the tissue at speeds 0.5, 1.0, and 1.5 mm/s. A continuous and transmural ablation line was recorded as successful. A 100% success rate was achieved at the pulmonary veins and the isthmus at some settings of energy delivery by the laser and RF. In the thick posterior right atrium, RF resulted in transmural lesions only when associated with carbonization, while the laser produced successful ablation lines in 100% of the attempts. In the left atrium, because of the presence of prominent trabeculations, RF was unsuccessful at all settings of energy delivery. In contrast, deep photocoagulation by laser resulted in successful ablations in the left atrium in 100% of attempts. Lesion formation was faster by laser ablation and mean lesion width was at least 25% smaller with the laser than with RF. In conclusion, the formation of linear lesions at the isthmus and at the pulmonary veins was successful with the laser and RF. In the trabeculated left atrium and the thick posterior right atrium, only laser ablation was successful.

Animals↗
PubMed2000

Circadian variation and onset mechanisms of ventricular tachyarrhythmias in patients with coronary disease versus idiopathic dilated cardiomyopathy.

To determine the circadian variations and the onset mechanisms of ventricular tachyarrhythmias (VT) in patients with implantable cardioverter defibrillators, stored electrograms of 364 VT episodes occurring in 40 patients with coronary artery disease (CAD) and in 29 patients with idiopathic dilated cardiomyopathy (DCM) were analyzed. A similar circadian distribution of VT episodes was observed in both groups, with a morning peak and less pronounced evening peak. After exclusion of patients with atrial fibrillation, VT onset was classified as (1) sudden if preceded by > or = 8 regular cycles without ventricular premature beats, (2) onset with a short-long-short interval, and (3) a more complex onset with variable patterns of ventricular premature beats before initiation of VT. Sudden onset was found in 26% and 21% of VTs in CAD and DCM respectively. A short-long-short interval preceded 29% of VTs in CAD compared to 14% of VTs in DCM (P < 0.05). A more complex onset was observed in the remaining 45% of VTs in CAD and 65% of VTs in DCM (P < 0.05). In conclusion, patients with DCM and CAD had similar circadian distributions of VT episodes. The majority of episodes were preceded by complex occurrence of ventricular premature beats rather than by the classic short-long-short sequence. These findings have important implications for the development of preventive pacing methods.

Cardiomyopathy, Dilated↗
PubMed2000

Relation between microvolt level T wave alternans and other potential noninvasive predictors of arrhythmic risk in the Marburg Cardiomyopathy Study.

The relation between microvolt level T wave alternans (TWA) and other noninvasive arrhythmia risk predictors was analyzed in 221 consecutive patients with idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg Cardiomyopathy Study between March 1996 and May 2000. TWA analysis was also performed in 110 healthy controls of similar age and sex. TWA during symptom-limited exercise was positive, negative and indeterminate in, respectively, 108 (49%), 65 (29%) and 48 (22%) patients with IDC versus, respectively, 5 (5%), 98 (89%) and 7 (6%) healthy controls (P < 0.05). Patients with IDC and positive TWA had a lower left ventricular (LV) ejection fraction (29 +/- 9% vs 34 +/- 10%, P < 0.05) and greater LV end-diastolic diameter (69 +/- 8 mm versus 64 +/- 6 mm, P < 0.05) than patients with negative TWA. Other variables, including age, gender, New York Heart Association functional class, presence of bundle branch block, arrhythmias on 24-hour ambulatory electrocardiogram, heart rate variability and baroreflex sensitivity, were not significantly different between patients with positive vs negative TWA. The prognostic significance of TWA in IDC with regard to arrhythmic events and total mortality will be determined by multivariate Cox analysis at the end of a 5-year follow-up in this ongoing study.

Adolescent↗
PubMed2000

Heart rate variability and baroreflex sensitivity in idiopathic dilated cardiomyopathy.

OBJECTIVE: To examine the relation between cardiac autonomic tone, assessed by baroreflex sensitivity and heart rate variability, and left ventricular function, arrhythmias on Holter monitoring, and clinical variables in patients with idiopathic dilated cardiomyopathy. DESIGN: A prospective observational study. PATIENTS: 160 patients with idiopathic dilated cardiomyopathy and preserved sinus rhythm in the absence of antiarrhythmic drug treatment. Measures of heart rate variability obtained by digital 24 hour Holter recordings included the mean of all coupling intervals between normal beats (RRm), the standard deviation of the mean of normal RR intervals (SDNN), and the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD). Baroreflex sensitivity testing was performed using the phenylephrine method. RESULTS: Mean SDNN (SEM) was 112 (46) ms, and baroreflex sensitivity was 7.5 (5.0) ms/mm Hg. SDNN showed a weak correlation with baroreflex sensitivity (r = 0.19, p < 0.05) and with left ventricular ejection fraction (r = 0.29, p < 0.05). SDNN showed no significant correlation with age (r = -0.07), the presence of non-sustained ventricular tachycardia (r = -0.13), or left ventricular end diastolic diameter (r = -0.07). In addition, baroreflex sensitivity showed no significant correlation with age (r = -0.13), non-sustained ventricular tachycardia (r = -0.08), left ventricular end diastolic diameter (r = 0.09), or ejection fraction (r = 0.14). CONCLUSIONS: The weak correlation between baroreflex sensitivity and heart rate variability suggests that these two indices explore different aspects of cardiac autonomic control in patients with idiopathic dilated cardiomyopathy. The weak or absent correlation between baroreflex sensitivity, heart rate variability, and other potential non-invasive risk predictors, including left ventricular ejection fraction, left ventricular end diastolic diameter, and non-sustained ventricular tachycardia on Holter monitoring, indicate that these variables may have independent prognostic value in idiopathic dilated cardiomyopathy.

Adolescent↗
PubMed2000

Antagonist/agonist balance of the nonsteroidal antiandrogen bicalutamide (Casodex) in a new prostate cancer model.

Androgen ablation is standard therapy for advanced prostate carcinoma. It can be administered either as a monotherapy or as a combined androgen blockade. In the present study we have investigated molecular mechanisms which are responsible for the development of resistance to therapy in advanced prostate cancer. For this purpose, we have cultured LNCaP cells in steroid-depleted medium for 1 year. The newly generated subline LNCaP-abl was characterized. In early passages (<75) LNCaP-abl cells showed a biphasic hypersensitive response to androgenic stimulation. Passages later than 75 are inhibited by androgen. Proliferation of LNCaP-abl cells was stimulated by the pure nonsteroidal antiandrogen bicalutamide (Casodex). To improve our understanding of changes which occur during intermittent androgen ablation, we have generated the sublines LNCaP-R (reversal; cultured with fetal calf serum) and LNCaP-RA (reversal and androgen; cultured with fetal calf serum and androgen) from LNCaP-abl cells. In both cell lines an increase of the basal proliferation rate was observed. Androgen receptor expression in LNCaP-abl cells was 4-fold higher than that in parental LNCaP cells (4.7 vs. 1.2 fmol/microg protein). Androgen receptor content in LNCaP-R cells was 1.8 fmol/microg protein and in LNCaP-RA cells 1.0 fmol/microg protein. The basal androgen receptor activity was 30-fold higher in LNCaP-abl cells compared to that in parental LNCaP cells. This basal activity was reduced in LNCaP-RA cells. Both androgen and the nonsteroidal androgen receptor antagonist hydroxyflutamide induced a 2- to 4-fold higher activation of androgen receptor in LNCaP-abl than in LNCaP cells. There was a switch from an antagonist to an agonist of the nonsteroidal antiandrogen bicalutamide (Casodex) in LNCaP-abl cells. Antagonistic properties of this androgen receptor blocker were again observed in both sublines (LNCaP-R and LNCaP-RA) derived from LNCaP-abl cells. In concordance with proliferation data in vitro, growth of LNCaP-abl cells in nude mice was stimulated by bicalutamide. In contrast, supplementation of androgen led to inhibition of proliferation of these cells. The present study provides new information that is useful for a better understanding of therapy-refractory prostate cancer. It is also important for the development of new therapy strategies for advanced carcinoma of the prostate.

Androgen Antagonists↗
PubMed2000

[FOITS (fast optical in vivo topometry of human skin): new approaches to 3-D surface structures of human skin].

FOITS (Fast Optical In-vivo Topometry of human Skin) is a new technique for the three-dimensional analysis of the microstructures of the skin. Based on the surface roughness standards used in the metal-working industry, it uses computer-assisted strip analysis to process information gathered from high-speed, non-contact scanning. It is possible to visualise the mathematical data in 3D form. So far, surface relief parameters have had to be acquired indirectly by first making silicone casts of the skin and then digitalising them with image analysis, mechanical scanners or, more recent, laser profilometry and confocal microscopy. We selected the roughness parameters Ra, Rz and Rmax (DIN defined) and "positive" and "negative" volume to describe the skin surface. In 40 healthy volunteers we were able to define significant intra-individual differences in these roughness parameters, which were correlated with the location of the area of skin being scanned (p < 0.05). When healthy areas of skin were compared with areas of chronic eczema in 10 patients with neurodermatitis the differences in the above-mentioned roughness parameters were just as striking (p < 0.05). In patients with chronic atopic eczema there was a statistically significant correlation between changes in the parameters "positive" and "negative" volume, and the smoothing of the skin seen after 14 days of treatment with standard ointments (p < 0.02). Apart from its industrial uses, we see potential applications for FOITS in the investigation of quantitative and qualitative aspects of aging processes, physiological and pathological processes in the skin, and the effect of topical preparations applied to the skin.

Adolescent↗
PubMed1999

Acute effects of LDL-apheresis on cholesterol oxidation products and antioxidants in plasma and lipoproteins of patients with familial hypercholesterolemia.

Regular LDL-apheresis treatment of hypercholesterolemic patients has proven to reduce the formation of atherosclerotic lesions. Regarding the underlying mechanisms, cholesterol oxidation products (COP) may play a detrimental role. Therefore, COP levels were determined before and after regular LDL-apheresis treatment in ten patients with familial hypercholesterolemia. - The patients had approximately twofold elevated plasma and LDL COP concentrations on the average as compared to healthy subjects. LDL-apheresis treatment efficiently removed COP from the circulation. As a consequence of a smaller reduction of the COP content (- 52 %) than of the total cholesterol content (-71 %) in LDL, the LDL COP:cholesterol ratio increased. Lipid-soluble antioxidants in the plasma of the hypercholesterolemics decreased to a comparable extent as did plasma lipids. In contrast to nearly stable vitamin C concentrations, plasma selenium concentrations also decreased, resulting altogether in a decreased but still normal serum total antioxidant capacity. - In conclusion, LDL-apheresis treatment effectively reduced potentially atherogenic COP from the plasma. With normal plasma antioxidant concentrations before LDL-apheresis in long-term treated hypercholesterolemics, the observed acute decrease in lipid-soluble antioxidants and selenium by treatment seems not to be as meaningful. The higher LDL COP:cholesterol ratio after treatment needs further elucidation.

Adolescent↗
PubMed1999

Heart rate variability in carcinoid heart disease.

Time domain heart rate variability measurements and echocardiographic studies were performed in 35 patients with carcinoid syndrome. Carcinoid heart disease was present in 18 patients (51%). Heart rate variability parameters (standard deviation of all normal RR intervals, percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms) were significantly reduced in patients with than in those without carcinoid heart disease.

Adult↗
PubMed1999

Toxicity of chromium to activated sludge.

The work deals with the toxicity of hexavalent and trivalent chromium to activated sludge. Cr(VI) was added as K2Cr2O7, and Cr(III) as Cr2(SO4)3. Toxicity is expressed as the inhibition of respiratory activity of microorganisms present in activated sludge. Respiration was measured by two methods, by means of an oximeter with an oxygen electrode and by means of a manometric apparatus permitting continuous observation of biological oxygen demand (BOD). The equation of the normal distribution function was used to construct inhibition curves and to calculate effective concentration (EC50). The influence of exposure time was observed as was the influence of concentration of activated sludge on the value of EC50. The 1-h EC50 for Cr(VI) by the ISO method was determined to be in the range of 40-90 mg/liter. A greater scatter of measured values, 46-201mg/liter, was found for the first hour of exposure by the manometric method. In the case of Cr(III) only combined inhibition by chromium ions and pH was determined. The 0.5-h EC50 was 49 mg/liter.

Bacteria↗
PubMed1999

Quantification of cardioprotective gene expression in porcine short-term hibernating myocardium.

Several cardioprotective proteins are induced during myocardial ischemia, such as heat shock proteins and anti-apoptotic Bcl-2-related proteins which, when experimentally overexpressed, have been shown to prevent ischemia-induced myocyte loss. As this pathophysiological induction is obviously not sufficient to prevent losses of myocytes, we analysed whether it could occur under moderate myocardial ischemia with hibernation, thus potentially contributing to myocyte protection under these conditions. Therefore, using anesthetized pigs with documented myocardial hypoperfusion and short-term hibernation, we investigated the left ventricular mRNA expression of the inducible heat shock protein Hsp70 and of the anti-apoptotic Bcl-XL in comparison with the pro-apoptotic Bak and Fas expression. For transcriptional analyses, the porcine cDNA sequences of Bcl-XL, Bak and Fas were identified by polymerase chain reaction (PCR) or by screening of a porcine heart cDNA library and cloned. Using reverse transcription polymerase chain reaction (RT-PCR), we observed an unchanged mRNA expression of inducible Hsp70, Bcl-XL, Bak and Fas after 85 min of hypoperfusion in the short-term hibernating myocardium, as well as after 30 min of subsequent reperfusion in the stunned myocardium, compared with transcription in a non-hypoperfused control area of the same ventricle. In conclusion, the mRNA expression of inducible Hsp70 and of several apoptosis-modulating proteins is not altered during moderate myocardial ischemia resulting in short-term hibernation of the affected area and during subsequent stunning.

Amino Acid Sequence↗
PubMed1999

Long-term stability of treatment results after upper jaw segmented osteotomy according to Schuchardt for correction of anterior open bite.

Upper jaw osteotomy according to Schuchardt is a relatively rarely performed surgical procedure due to its narrow range of indications. Within the framework of a clinical follow-up examination using this method, we studied the long-term results in 26 patients, employing cephalometric analysis and analyzing the clinical findings. The results of this study show that the outcome of the operative correction of anterior open bite remained largely stable. Although partial relapse occurred in 3 cases (= 11.5%), there was a significant functional and esthetic improvement in comparison with the preoperative initial findings. When indicated, upper jaw osteotomy according to Schuchardt is thus a suitable surgical technique for correction of anterior open bite.

Adolescent↗