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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 325 records · Page 18Linked to original sources

Single amino acid changes that render human IFN-alpha 2 biologically active on mouse cells.

Human IFN-alpha 1 and IFN-alpha 2 differ in 28 of 166 amino acids and show very different specific antiviral activities on human and murine cells. We have identified, by hybrid scanning and site-directed mutagenesis, three residues in IFN-alpha 2, in positions 121, 125 and 132 which, when replaced individually or jointly by their IFN-alpha 1 counterparts, modify its activity on mouse cells by up to 400-fold. We argue that these residues are involved in direct contacts with the mouse interferon receptor.

Amino Acid Sequence↗

Genetic analysis of the gene ICL1 of the yeast Yarrowia lipolytica.

The gene ICL1 codes for the tetrameric enzyme isocitrate lyase of Y. lipolytica. Twenty icl1- alleles have been analysed for their reversion frequency, their interallelic complementation pattern, and the position of the corresponding mutation site on the fine structure map of the gene ICL1. One intragenic temperature-sensitive revertant of the allele icl1D-39 was isolated, which expressed a thermolabile enzyme. In spite of the fact that nonsense mutations have been detected, the direction of transcription of the gene ICL1 was inferred from the localization of a linked cis-dominant regulatory mutation site. The size of the mitotic map of this gene suggests that recombination frequency in Y. lipolytica is lower than in Saccharomyces cerevisiae.

Alleles↗

Neuronal representation of spectral and spatial stimulus aspects in foveal and parafoveal area 17 of the awake monkey.

We have recorded from 661 single neurons in the foveal and parafoveal region of area 17 of the awake trained macaque monkey. The functional properties of 538 cells were investigated in detail, with flashed and moving stimuli of varying form and colour. Irrespective of their functional properties such determined, each neuron was also tested with a 2 X 2 degrees square of various luminance and colour. This was done in order to get an idea how such a simple stimulus is represented by the activities of neurons in area 17. Most of the neurons showed response preference for certain aspects of visual stimuli. We have distinguished the following functional groups: 1. Sustained spectrally selective neurons (21%). These cells respond with tonic discharges to light of their optimal wavelength, and their spectral selectivity corresponded to that of opponent parvocellular cells of the lateral geniculate body. 44% of these cells were excited selectively by long, 23% by middle and 33% by short wavelength light. When slowly moving the 2 X 2 degrees square of their preferred wavelength across the receptive field, discharge rate remained elevated, as long as the stimulus covered the RF and with little contour enhancement. The majority of the sustained spectrally sensitive cells responded equally well or better to large than to small (1.0 degree) stimuli, 17.5% were less activated and few of them completely suppressed by larger stimuli. Such cells were poorly orientation sensitive. Only three cells with weak double opponency could be identified (2.7% of this group). 2. Broadband contour (18%) and 3. Panchromatic contour cells (41%). Most neurons of these two groups were strongly activated by spots (1 degree) centered on their RF. They showed a short phasic response to contrast borders and most of them responded to luminance contrasts, including contrast reversal and colour contrasts equated for luminance. The broadband contour cells showed a slight wavelength preference with only weak or without any opponent suppression, the panchromatic contour neurons did not show any wavelength selectivity. Most showed orientation or direction sensitivity, but very sharp orientation selectivity was less common in spectrally biassed than in panchromatic contour cells (see Fig. 11). They responded tonically to gratings of optimal orientation and therefore may play a role also for cortical representation of textures. 22% of a restricted sample of panchromatic contour cells (or 9% of all cells) were hypercomplex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Behaviour of heart rate and electrical muscle activity in the simultaneous dynamic action of larger and smaller sets of muscles in the permanent performance threshold range.

This study was undertaken to assess more comprehensively and with greater differentiation the reduction in the absolute electrical muscle activity (aEA) determined by different investigations in the permanent performance threshold range of the cardiovascular system (HKS) by means of the behaviour of the aEA of the highly stressed leg muscles and little stressed forearm muscles. Six healthy, untrained male subjects operated a hand ergograph alone in one test, and, in four more tests, in combination with a constant bicycle ergometer load of 40, 60, 80, and 100 W, respectively. As a result of these tests, a relative reduction in aEA for the leg muscles and an absolute reduction in aEA for the forearm muscles could be identified in the permanent performance threshold range of the HKS. Therefore, aEA is also considered to be an indicator of general stress that can define the permanent performance threshold range of the HKS more completely. The reduction in aEA is probably an expression of a negative feedback from the cardiovascular system to the neuromuscular system induced by the central nervous system.

Adult↗

Potential life-threatening cardiac arrhythmias associated with a conventional hypocaloric diet.

Nine obese children (mean age 12.7 years, mean overweight 74.2%) were treated for 3 weeks with a very low calorie diet containing high quality protein. Eight patients (patients A) received a commercially available diet (240 kcal/1004 kJ/day) and 1 patient (patient B) a homemade dietary regimen (500 kcal/2100 kJ/day). Both preparations were supplemented with micronutrients; however, the daily intake of minerals was significantly less in patient B. All patients were monitored for the appearance of cardiac arrhythmias by frequent 24-hour Holter recordings. In patients A the mean loss of body weight was 9.4 +/- 2.4 kg, patient B lost 8.7 kg. The mean daily nitrogen balance was negative (patients A: 10.2 g/day, patient B: 6.8 g/day). Frequent blood chemistry evaluations were unremarkable. On the 14th day of treatment patient B developed arrhythmias (ventricular couplets, non-sustained ventricular tachycardias); in patients A no ventricular dysrhythmias were observed. Our data suggest that very low calorie diets containing protein of high biologic value can be associated with potentially dangerous arrhythmias.

Adolescent↗

Sudden death during ambulatory Holter monitoring.

Four cases of sudden cardiac death during ambulatory Holter monitoring are described. All had coronary arterial disease. Two patients were on antiarrhythmic drug therapy and both had a prolonged QTc-interval on their resting electrocardiogram. The predominant rhythm was sinus rhythm in all. In one patient, severe bradycardia terminated in asystole. In the remaining 3 patients, ventricular flutter (which was initiated in 2 instances by a short run of polymorphous ventricular tachycardia) degenerated into ventricular fibrillation. The lethal event was triggered once by an early cycle ventricular premature beat and twice by late cycle ventricular premature beats. There was no specific pattern of warning arrhythmias preceding sudden cardiac death. Signs of ischemia/sympathetic overactivity preceding sudden cardiac death were found in 3 patients. Autopsy studies were performed in 2 patients and revealed acute ischemic myocardial damage.

Aged↗

IS431, a staphylococcal insertion sequence-like element related to IS26 from Proteus vulgaris.

We present the nucleotide sequence of IS431, a new staphylococcal insertion sequence-like element flanking the mercury-resistance determinant of pI524 and associated with the methicillin-resistance determinant. IS431 left is 800 bp long and has a perfect terminal inverted repeat (IR) of 22 bp; IS431 right is 786 bp long and has a terminal IR homologous to the IR of IS431 left except that the terminal 8 bp are absent. Both IRs share a 10-bp homology with the IR of IS26 from Proteus vulgaris. No directly repeated sequences were detected immediately adjacent to the IRs. An open reading frame (ORF) of 675 bp spans most of the IS431 sequence. Its deduced amino acid (aa) sequence shows 40% homology to the 234-aa-long putative transposase coded by ORFI of IS26.

Animals↗

Fluorine-19 NMR spectroscopic studies of the metabolism of 5-fluorouracil in the liver of patients undergoing chemotherapy.

Fluorine-19 nuclear magnetic resonance allows direct observation of fluorinated drugs and their metabolites in the human body without background signal from the tissue. A well-known fluorinated chemotherapeutic drug, 5-fluorouracil, and its metabolites were observed noninvasively in the liver of three patients undergoing cancer chemotherapy. Spectra were obtained at 1.5 T with a surface coil centered over the right lobe of the patient's liver. Administration of 1.5 gm of 5-fluorouracil was done after positioning in the magnet. Serial spectra, collected over a 2-h period, revealed both the nature of the metabolites present in the liver, and the time course of each patient's metabolism. These observations represent the first noninvasive NMR study of drugs in human patients and show the feasibility of using in vivo F-19 NMR spectroscopy for human studies of fluorinated compounds.

Female↗

Vidarabin-monophosphate, BCNU, VM26--an in vitro comparative study of active agents in the treatment of malignant human brain tumours.

BCNU (carmustine), VM26 (teniposide) and ARA-A5'P (vidarabin-monophosphate) were compared in their activity against 30 cell lines of primary (N = 21) and metastatic (N = 9) human brain tumours, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products c X t were correlated with in vitro pharmacokinetic data in order to evaluate in vitro drug sensitivity at relevant exposure doses. A microcytotoxicity assay was employed to screen for drug toxicity in individual tumour cell lines. Following drug exposure and 5 to 8 population doubling times of untreated controls, RNA-synthesis - as a parameter of cell metabolism and proliferation - was determined by incorporation of [5,6-3H]-uridine into cellular RNA (liquid scintillation counting protocol). The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index (SI); by these means effects of different drugs on individual tumour cell lines could be compared. Mean sensitivity indices of ARA-A5'P, BCNU and VM26 for primary brain tumour cell lines were 0.59, 0.82 and 0.54. ARA-A5'P and VM26 had almost similar activities against brain tumour cell lines, whereas BCNU was significantly (P less than 0.001) less active. High grade gliomas were less sensitive to all three agents than low grade and infratentorial gliomas. ARA-A5'P was also able to effectively reduce colony formation in brain tumour cell lines. A cross-resistance of ARA-A5'P to either BCNU or VM26 could not be observed. Clearly, ARA-A5'P is an effective drug in treatment of brain tumour cells in vitro.

Adolescent↗

[Experimental research with a new percutaneously insertable and expandable vascular prosthesis].

Restenosis and occlusion are the most common reasons why transluminal balloon angioplasty may fail to provide long-term benefit. To prevent restenosis and occlusion of diseased arteries after angioplasty an arterial endoprosthesis has been developed which is positioned to the balloon of an angioplasty catheter and which consists of a stainless steel pliable and elastic tube. With the inflation of the balloon the endoprosthesis will dilate and give the arterial wall a new mechanical support. This new device has been implanted in 12 experimental dogs in arteries of different size and lumen. The longest patency rate of nine months was observed with the completely developed method.

Angioplasty, Balloon↗

Evaluation of esophageal tracheal combitube in cardiopulmonary resuscitation.

Prompt establishment of an airway is a primary goal in CPR of nonbreathing and unconscious patients. The esophageal tracheal combitube (ETC) is a new airway, designed for emergency intubation providing sufficient ventilation whether the airway is placed into the trachea or into the esophagus. We evaluated the effectiveness of the ETC in 31 patients during CPR. Blood gas analyses obtained during esophageal placement of the ETC showed results comparable to those of ventilation with a conventional endotracheal airway (ETA). The ETC appeared to oxygenate and ventilate patients adequately without complications. The efficacy, safety, and ease of insertion ensure rapid airway control. It is concluded that the ETC provides a sufficient alternative to the ETA whenever ideal conditions or trained staff for endotracheal intubation are not immediately available.

Aged↗

Treatment of acute low-back pain with piroxicam: results of a double-blind placebo-controlled trial.

Twenty-seven investigators participated in a double-blind, parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain. Therapy commenced within 48 hours of the injury and continued for 7 days. The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter. After 3 days of therapy, piroxicam patients showed a statistically greater amount of pain relief in the lying (P less than 0.001), sitting (P less than 0.01), and standing (P less than 0.01) positions, but after 7 days the difference between treatments was no longer significant. After 1 week's therapy, however, the requirement for additional analgesic was significantly lower in the piroxicam group (P less than 0.05), and more piroxicam than placebo patients (42 versus 28) had returned to work (P less than 0.05). Toleration was excellent in most patients, with only 13% of the piroxicam and 17% of the placebo group reporting adverse effects of mainly mild or moderate severity. The profile of the adverse effects was similar for both treatments. Piroxicam can provide effective relief of acute low-back pain with good toleration; it should be considered for use in the initial treatment of this condition.

Acute Disease↗

Therapy of malignant brain tumors: comparison of the in vitro activities of vidarabin-monophosphate, BCNU and 5-fluorouracil.

BCNU (carmustine), 5-Fluorouracil (5-FU) and Vidarabin-monophosphate (ARA-A5'P) were compared in their activities against 30 cell lines of primary (n = 21) and metastatic (n = 9) brain tumors, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products were correlated with in vitro pharmacokinetic data. A micro assay was employed to screen for drug toxicity in individual tumor cell lines; cells were exposed to the drugs at exposure doses relevant to in vivo pharmacokinetics. After 5-8 population doubling times of untreated controls, RNA-synthesis, as a parameter of cell metabolism and proliferation, was determined by incorporation of (5, 6-3H)-uridine into cellular RNA (liquid scintillation counting protocol). A tumor stem cell assay was performed under similar conditions. The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index SI (SI = 1 indicating complete resistance) to compare effects of different drugs on the individual tumor cell lines. Mean sensitivity indices for ARA-A5'P, BCNU and 5-FU in brain tumor cell lines (in brackets: primary CNS-tumors) were 0.64 (0.59), 0.89 (0.82) and 0.35 (0.33) respectively. 5-FU was significantly more active than BCNU and ARA-A5'P (P less than 0.001), whereas BCNU was significantly less active than ARA-A5'P (P less than 0.001). ARA-A5'P had a suppressive effect on formation of brain tumor stem cell colonies. There was no cross-resistance of ARA-A5'P to either BCNU or 5-FU. We conclude that ARA-A5'P and 5-FU are potent agents in experimental therapy of human brain tumors, compared with BCNU.

Brain Neoplasms↗

Surface coil with variable geometry: a new tool for MR imaging of the spine.

A switchable-array surface coil for magnetic resonance (MR) imaging of the spine has been built that enables the user to change the working size of the coil depending on the volume of interest. The prototype has achieved similar image quality to that obtained with conventional coils of equal size. This type of antenna may reduce the number of individual coils necessary for a high-quality MR imaging study.

Humans↗

Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, VI. Nucleotide sequences of lactate dehydrogenase genes from the thermophilic bacteria Bacillus stearothermophilus, B. caldolyticus and B. caldotenax.

Based on the previously determined amino-acid sequence of lactate dehydrogenase from B. stearothermophilus, an oligonucleotide probe was synthesized and used to clone the structural genes for lactate dehydrogenase from B. stearothermophilus, B. caldolyticus and B. caldotenax. The nucleotide sequences of the entire LDH genes from these three thermophilic bacilli were determined by the method of Maxam and Gilbert. The nucleotide sequence of the LDH gene from B. stearothermophilus is exactly identical to the one published recently; it agrees with the experimentally determined amino-acid sequence except at three positions. The amino-acid homologies among these thermophilic enzymes are 90% or more. The LDH genes are efficiently expressed in E. coli.

Amino Acid Sequence↗