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H Gruber

Publications and source records attributed to H Gruber.

At least 19 recordsLinked to original sources

The nitrate reductase-encoding gene of Volvox carteri: map location, sequence and induction kinetics.

The nitrate reductase (NR) structural gene (nitA) of Volvox carteri has been cloned and characterized. There is a single copy of this gene in the genome, and RFLP (restriction-fragment length polymorphism) analysis assigns it to the previously defined nitA/chlR locus on linkage group IX, 20-30 cM from the two beta-tubulin-encoding loci. Determination of the 5871-nt sequence of the coding region of genomic clones, and comparisons to a cDNA sequence, revealed ten introns and eleven exons that encode a 864-aa polypeptide. Detailed comparisons with higher-plant and fungal NRs indicate that, whereas the aa sequence is strongly conserved within functional domains for the flavin adenine dinucleotide-, heme- and molybdenum-pterin cofactor-binding sites, substantial differences in the aa sequence occur in the N-terminal end and the two inter-domain regions. Two potential transcription start points 439 and 452 nt upstream from the start codon and a polyadenylation signal 355 nt downstream from the stop codon have been identified by primer-extension analysis and cDNA sequencing, respectively. Accumulation of the nitA transcript is both induced by nitrate and repressed by ammonium and urea: after the organism is transferred from ammonium to nitrate as the nitrogen source, a 3.6-kb NR transcript is readily detectable on Northern blots by 10 min, reaches maximum abundance by 30 min, and then rapidly declines to an intermediate level that is subsequently maintained. Substantial induction by nitrate is observed at the end of the dark portion of the daily light/dark cycle, but the inductive response peaks in the first hour of the light period.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Reduction of the compact and cancellous bone substances of the edentulous mandible caused by resorption.

Examination of various bone sections of edentulous atrophic mandibles showed that the body of the mandible loses up to 60% of its original bone substance during progressive atrophy. Most of the bone loss occurs in a relatively early stage of the atrophic process. The greatest extent of bone reduction can be observed in the area of the second premolar and the first molar. In the interforaminal region, which is situated mesial from them, resorption, in most cases, is not as progressive as in the premolar/molar area. The compact and cancellous bone substances are most often equally affected by resorption. Moreover, it could be observed that the cancellous bone substance of extremely atrophic mandibles particularly in the interforaminal region, is marked by a significant increase in density. This might be interpreted as a restructuring process to compensate for bone losses and to secure the stability of the atrophic body of the mandible.

Alveolar Bone Loss

Preliminary clinical experience with polyurethane vascular prostheses in femoro-popliteal reconstruction.

Following promising results in animals, implantation of polyurethane vascular prostheses for femoral reconstruction was performed in 15 patients over a 10-month period. This prospective study was carried out to evaluate the patency, limb salvage and complications associated with this type of small diameter conduit for arterial occlusive diseases. The indications for surgery included acute and chronic ischaemia, non-healing ulceration or gangrene. There were five early occlusions, which resulted in a 1-month primary patency rate of 66% and a secondary patency rate of 80%. The mean limb salvage rate at 1 month was 80% and is 66% at the present time. Infection occurred in one patient following multiple attempts at graft thrombectomy. There were no statistically significant differences in patency rates between proximal and distal popliteal graft anastomoses. Two critical phases of healing were identified where the graft was prone to flow deterioration; at 4-6 weeks and at 4-6 months. It is concluded that although this type of graft has many interesting features, e.g. the presence of endothelial cells under poor haemodynamic conditions, excellent graft-host healing and good resistance at the suture site, further investigations on protein absorption and complement activation as well as intensive structural testing are required before further recommendations can be made.

Aged

Time course of histomorphometric alterations in nerve grafts without connection to a muscle target organ: an experimental study in sheep.

In 15 adult sheep, the saphenous nerve (28 +/- 1.8 cm) was used for ipsilateral or for cross-nerve grafting and was sutured to the proximal stump of the cut, motor-nerve branch of the vastus muscle. The distal end of the nerve graft was left without a target organ. Semi-thin cross sections of normal vastus nerves and saphenous grafts and of the distal ends of the grafts were analyzed by computer-assisted planimetry, 3, 6, 9, 12, and 18 months after the nerve-grafting procedure. Electronmicroscopy was also performed on specimens from the distal ends of the nerve grafts. Comparing the total number of myelinated nerve fibers in the distal end of the graft, the ipsilateral group showed an increase with time elapsed since nerve grafting, while the cross-over group showed a maximum after 3 and 6 months, and fewer fibers after longer periods of regeneration. Independent of the time passed since nerve grafting, the diameters of the myelinated nerve fibers were homogeneously thin in both experimental groups. Most interesting, the cross-nerve grafts did more poorly than the ipsilateral ones, even before they were influenced by the target muscle. With ultrastructural investigation, the ends of the grafts containing only a few myelinated fibers also showed a low number of unmyelinated fibers, but an increase of collagen fibers. The results have consequences for the clinical application of cross-nerve grafting.

Animals

Long-term results of nervous tissue alterations caused by epineurial electrode application: an experimental study in rat sciatic nerve.

In order to evaluate the long-term effects of epineurial electrode application for functional electrical stimulation (FES) the left sciatic nerve of seven rats was exposed. Four ring-shaped stainless steel wire electrodes were sutured to the epineurium of each nerve in the same manner as performed clinically for carrousel stimulation in man. The nerves were reexposed 1 year after implantation and the stimulation threshold to obtain a tetanic contraction in the lower limb was determined for each electrode. Afterwards the animals were sacrificed. The electrodes were excised and cross sections of the sciatic nerve directly at site of the electrodes, 2-mm proximal and 2-mm distal to them were harvested for histologic and planimetric assessment of nerve lesions. The area of damaged neural tissue was expressed as a percentage of the total cross-sectional area within the perineural sheath. The sciatic nerves of the right side served as controls. The values for the stimulation thresholds ranged between 0.1 and 1.0 mA (mean 0.43 mA). By morphometric examination five of seven nerves were seen altered, the altered areas captured between 1% and 4.8% of the total cross-sectional area of the nerves within the perineural sheath. Besides two specimens, all altered nerve segments exhibited distinct signs of nerve fiber regeneration. The clinical implications of the results for long-term electrical stimulation, such as phrenic pacing, are discussed.

Animals

AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent.

AICA-riboside (5-amino-4-imidazole carboxamide ribonucleoside) is a novel adenosine-regulating agent that is currently being investigated for the treatment of ischemic heart disease. In a placebo-controlled, double-blind study in healthy men, we evaluated the safety and kinetics of the drug after oral and IV administration of 10, 25, 50, and 100 mg/kg doses. At each dose level, four subjects received active drug and two subjects received placebo with a 1-week wash-out period between the IV and oral doses. The drug was well tolerated at all dose levels with only mild and transient side effects reported in some instances by the subjects who received placebo and those patients who received the drug. The post-infusion plasma concentrations of AICA-riboside declined rapidly in a biphasic fashion, and the terminal elimination phase had a harmonic mean t1/2 beta of 1.4 hours. Total plasma clearance (CL), mean residence time (MRTIV), and volume of distribution at steady-state (VSS) were 2.5 L/hr/kg, 0.7 hr, and 1.6 L/kg, respectively. The drug was not protein bound, and there was rapid uptake and phosphorylation in RBCs to its 5'-monophosphate nucleotide. Renal clearance (CLR) was 0.2 L/hr/kg with only 8% of the IV dose excreted in the urine as intact AICA-riboside. Although there was a trend towards a decrease in CL with increasing dose, there were no significant differences (P greater than .05) in the mean estimates of t1/2 beta, CL, CLR, MRTIV and VSS associated with dose. The drug was poorly bioavailable (less than 5%) when administered orally in solution.

Administration, Oral

Histomorphometric studies in patients with facial palsy treated by functional muscle transplantation: new aspects for the surgical concept.

Whenever it was possible, muscle and nerve biopsies were performed in patients with irreversible, unilateral facial palsy treated by cross-face nerve grafting and free gracilis muscle transplantation with microneurovascular anastomoses. Planimetric analyses of cross-sections showed the following, to some extent, surprising, results: (1) Independent of the final functional result, approximately the same number of regenerated, thin nerve fibers (100-200) were found in the distal end of the cross-face nerve graft at the time of muscle transplantation. These are approximately 20% of the nerve fibers counted in the branches of the facial nerve at the healthy side used for reinnervation. (2) There is no correlation between the number or diameter of the nerve fibers in the distal end of the cross-face nerve graft and the functional recovery of the transplanted muscle, but there is good correlation between the morphology of the fibers of the muscle graft and the functional result. (3) Different portions of slow-contracting and fast-contracting muscle fibers in the reinnervated muscle grafts showed the strong influence of the quality of the nerve used for the crossover innervation. If a facial nerve branch innervating the slow buccinator muscle was used, the originally fast gracilis muscle was transformed to a slow muscle by this kind of reinnervation. These important findings are the basis of a new view of surgery in the treatment of irreversible facial palsy by functional free-muscle transplantation.

Biopsy

The TraM protein of plasmid R1 is a DNA-binding protein.

The TraM protein of the resistance plasmid R1 was purified to homogeneity and used for DNA-binding studies. Both gel retardation- and footprint experiments showed that TraM specifically binds to DNA of plasmid R1 comprising the region between the origin of transfer and the traM gene. Several TraM molecules bind and, according to the footprint experiments, two distinct sites of specific binding exist. The two sites are separated from each other by 12 nucleotides and each contains an inverted repeat. DNase I protection assays showed that the initial TraM binding occurs at these palindromic sequences. At higher protein concentrations the lengths of the DNA segments protected by TraM were increased towards the traM gene. In one region this extension leads to binding of TraM protein at its own promoters.

Bacterial Proteins

First experimental application of multichannel stimulation devices for cardiomyoplasty.

The effect of long-term application of epineural electrodes to nerves was investigated in rat experiments. Neural damage reached a maximum of 6% shortly after implantation and decreased to 3% after 1 year. Impedance and threshold of epineural electrode were investigated in sheep experiments for up to 12 months. The mean impedance was in the range of 1 kohm, while the threshold less than 1 mA. The reduction in fatigue produced by multichannel stimulation was demonstrated by sequential isometric contractions of rectus muscles in sheep. The decrease in force was only 10% after 60 minutes of multichannel stimulation as compared to a reduction of 50% for single channel stimulation. Studies of cardiomyoplasty with single channel stimulation confirmed results reported by other investigators. In acute experiments with sheep, we demonstrated fiber-selective stimulation which led to isolated contraction of the left or right distal part or the right proximal part of the latissimus dorsi muscle. Potential advantages in the application of implantable multichannel stimulation devices as compared to single channel stimulation for cardiomyoplasty include: (1) fatigue-free stimulation at submaximal force level; (2) selection of hemodynamically effective electrode combinations; (3) potential for consecutive activation of muscle fiber groups, thereby allowing better simulation of the physiological contraction of the heart muscle; (4) redundancy of electrodes in case of technical failure or dislocation; and (5) stimulation of more than one muscle, if necessary.

Animals

Histological assessment of nerve lesions caused by epineurial electrode application in rat sciatic nerve.

The left sciatic nerve of 36 rats was exposed and four ring-shaped stainless steel wire electrodes were sutured to the epineurium of each nerve in the same manner as performed clinically for "carousel stimulation" in man. The rats were sacrificed 10 days (Group 1), 3 weeks (Group 2), or 3 months (Group 3) after implantation. The electrodes were excised, the nerves were embedded in Epon, and semithin sections were obtained for histological and planimetric assessment of lesions caused by the epineurially sutured electrodes. The right sciatic nerves served as controls. The total area of neural tissue within the perineurium was determined at three levels: at the site of the electrodes, 8 mm proximal, and 8 mm distal. The area of neural tissue damaged by the surgical procedure was expressed as a percentage of the total area. In Group 1, nine of 12 nerves showed lesions ranging from 0.39% to 25.39% of the total area of neural tissue, in Group 2 eight of 11 sciatic nerves showed lesions ranging from 0.24% to 13.03% of the total area, and in Group 3 five of 12 nerves showed lesions ranging from 0.21% to 4.96% of the total area. The pathologically altered areas in Groups 2 and 3 exhibited distinct signs of nerve fiber regeneration. The reasons for the decrease in damage from Group 1 to Group 3 and the clinical implications of the results for long-term electrical stimulation are discussed.

Animals

Adrenal carcinosarcoma.

The clinical and pathologic features of a case of adrenal carcinosarcoma are reported. Although synchronous malignancy of the adrenal gland has been described, no case of an adrenal tumor combining both carcinomatous and sarcomatous elements has been previously documented. This neoplasm is extremely aggressive with distant metastasis arising from the sarcomatous component, and rapid progression despite multimodal therapy.

Adrenal Cortex Neoplasms

[Computed perimetry for the follow-up of optic neuropathy in pseudotumor cerebri].

Computerized static perimetry must be regarded as the method of choice for monitoring the course of optic neuropathy in cases of pseudotumor cerebri. A discrete peripheral visual field depression is the first sign of optic nerve damage. If cranial hypertension persists the visual field depression gradually spreads toward the center. Ultimately central visual acuity deteriorates continuously. If the intracranial hypertension is reduced in good time the visual field defects are largely reversible and optic atrophy can be prevented.

Diagnosis, Computer-Assisted

[Changes in visual evoked potential latencies following retrobulbar neuritis].

After unilateral retrobulbar neuritis, VEP latency time does not remain stable: in 7 out of 9 patients, significant changes in latency time were recorded after intervals of 15 to 35 months. In 6 of the 9 cases a reduction in latency time was observed, in 2 of them complete normalization. In one patient it increased further as compared to the initial examination. One conclusion from these findings is that optic neuritis in remission cannot be ruled out by normal VEPs.

Adult

Ipsilateral and cross-over elongation of the motor nerve by nerve grafting: an experimental study in sheep.

In difficult reconstructions, ipsilateral or cross-over nerve grafting is sometimes necessary to achieve reinnervation and motor function. This experimental study in sheep was to answer the question of limitation of elongation of a motor nerve by grafting, the question of the optimal time for suturing the nerve graft to the muscle nerve, and the question of the successful application of this surgical technique in extremities. In 18 sheep, the vastus nerve was elongated by a saphenous nerve graft as long as possible up to 30 cm (step 1). In 10 animals the nerve graft was applied ipsilaterally, and in 8 animals it was used as a cross-over nerve graft to the contralateral limb. The time between nerve grafting and connection of the distal end of the nerve graft to the freshly cut rectus nerve supplying the rectus femoris muscle (step 2) was variable: 0, 3, 6, 9, and 12 months. In all animals, the final experiments (step 3) were performed 6 months after the last operation (step 2). Muscle force measurements in the rectus femoris muscle and quantitative analysis of the number and diameter of myelinated nerve fibers in cross sections of the nerve biopsies at different levels showed that elongation of a motor nerve by nerve grafting is principally not limited. The functional results were rather inhomogeneous and therefore unpredictable (ipsilateral group: maximum tetanic tension = 27 to 172 N; cross-over group: 0 to 227.5 N). Nevertheless, crossover nerve grafting is recommended for selected cases even in extremities. There was no correlation between the time interval between the two operations and the functional or morphologic results, although better functional results were obtained when the distal nerve suture (step 2) was performed some months after nerve grafting (step 1). A clear correlation was found only between the number of regenerated axons in the rectus nerve behind the second suture line and the muscle function.

Animals

Histochemical mapping and fiber size analysis of mimic muscles.

Fourteen functionally relevant mimic muscles of nine human bodies were analyzed with respect to their muscle fiber sizes and their histochemical fiber type composition. In cryostat sections stained for actomyosin ATPase, type 1 and type 2 fibers were evaluated separately by means of computer-assisted image analysis. The fiber diameters varied between 20.24 and 41.45 microns. According to the proportions of the fiber types, the mimic muscles could be classified into three groups: (1) phasic muscles, with 14 to 15 percent type 1 fibers, (2) intermediate muscles, with 28 to 37 percent type 1 fibers, and (3) tonic muscles, containing 41 to 67 percent type 1 fibers. It is concluded that one has to consider this diversity of mimic muscles when planning the surgical reconstruction of facial paralysis.

Adult

Neuromuscular diseases: evaluation with high-frequency sonography.

Forty-four patients with clinically suspected neuromuscular disease and 12 healthy volunteers underwent high-frequency ultrasound examination of the rectus femoris, vastus medialis, vastus lateralis, and biceps brachii muscles, and the number of perimysial septa was determined. These numbers and muscle/soft-tissue ratios of the lower extremity were compared. Findings were correlated with results of muscle biopsy in all patients with suspected disease. Using the number of perimysial septa in the lower extremity, the authors found significant differences between the muscles of healthy volunteers and those of patients with Duchenne muscular dystrophies, other muscular dystrophies, and spinal muscular atrophies: The receiver operating characteristic curve showed that an average of 12 perimysial septa within 1 cm of muscle is the ideal cutoff value to differentiate subjects without morphologic changes from those with pathologic findings. The authors conclude that this measurement is useful for differentiation of neuromuscular diseases and may be a noninvasive, reproducible means with which to evaluate disease progression.

Adolescent