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Biomedical subjects

M Herzog

Publications and source records attributed to M Herzog.

At least 19 recordsLinked to original sources
PubMed2003

[Long term results after cochlear implantation in elderly patients].

BACKGROUND: Cochlear implantation has become the method of choice for the treatment of deaf patients. A better technology of stimulation opened a wider field of patients suitable for cochlear implantation. Aim of the present study was to evaluate to which extent senior patients benefit by cochlear implantation. PATIENTS AND METHODS: 36 patients between 65 and 85 years were tested by the Freiburger speech test for monosyllabic words and by the HSM sentence test with and without noise. The results were compared to those of younger implanted patients (16 - 64 years, n = 101). RESULTS: The speech perception for monosyllabic words did not differ significantly between both groups. A maximum plateau in speech perception for monosyllabic words was reached after 2 years at 55 %. The HSM sentence test revealed significant differences in the increase of speech perception between senior and younger patients in the first post surgical year. After one year elderly patients reached the same perception score as younger patients with a maximum of approximately 80 % after 3 years. At a signal to noise ratio of 15 % younger patients achieved a maximal perception of 55 % after 1 year whereas senior patients needed 4 years to reach this level. CONCLUSIONS: Senior patients benefited by cochlear implantation to the same extent as younger patients did. Senior patients gained a similar speech perception level as younger implanted patients although the elderly needed more time to reach the same scores. Nevertheless, cochlear implantation should not be denied due to age alone.

Aged↗
PubMed2002

CGRP receptors in the gerbil spiral modiolar artery mediate a sustained vasodilation via a transient cAMP-mediated Ca2+-decrease.

Alteration of cochlear blood flow may be involved in the etiology of inner ear disorders like sudden hearing loss, fluctuating hearing loss and tinnitus. The aim of the present study was to localize the vasodilator calcitonin gene-related peptide (CGRP) and to identify CGRP receptors and their signaling pathways in the gerbil spiral modiolar artery (SMA) that provides the main blood supply of the cochlea. CGRP was localized in perivascular nerves by immunocytochemistry. The vascular diameter and cytosolic Ca2+ concentration [Ca2+]i in the smooth muscle cells were measured simultaneously with videomicroscopy and fluo-4-microfluorometry. Calcitonin receptor-like receptor (CRLR) mRNA was identified by RT-PCR as a specific 288 bp fragment in total RNA isolated from the vascular wall. The SMA was preconstricted by a 2-min application of 1 nM endothelin-1 (ET1). CGRP, forskolin, and dibutyryl-cAMP caused a vasodilation (EC50 = 0.1 nM, 0.3 mM, and 20 mM). CGRP and forskolin caused an increase in cAMP production and a transient decrease in the [Ca2+]i. The CGRP-induced vasodilation was antagonized by CGRP8-37 (KDB = 2 mM). The K+-channel blockers iberiotoxin and glibenclamide partially prevented the CGRP- or forskolin-induced vasodilations but failed to reverse these vasodilations. These results demonstrate that CGRP is present in perivascular nerves and causes a vasodilation of the ET1-preconstricted SMA. The data suggest that this vasodilation is mediated by an increase in the cytosolic cAMP concentration, a transient activation of iberiotoxin-sensitive BK and glibenclamide-sensitive KATP K+ channels, a transient decrease in the [Ca2+]i and a long-lasting Ca2+ desensitization.

Animals↗
PubMed2001

CPR5 is involved in cell proliferation and cell death control and encodes a novel transmembrane protein.

Plants often respond to pathogens by sacrificing cells at the infection site. This type of programmed cell death is mimicked by the constitutive pathogene response5 (cpr5) mutant in Arabidopsis in the absence of pathogens, suggesting a role for CPR5 in programmed cell death control. The analysis of the cellular phenotypes of two T-DNA-tagged cpr5 alleles revealed an additional role for CPR5 in the regulation of endoreduplication and cell division. In cpr5 mutant trichomes, endoreduplication cycles stop after two rounds instead of four, and trichome cells have fewer branches than normal. Eventually, cpr5 trichomes die, the nucleus disintegrates, and the cell collapses. Similarly, leaf growth stops earlier than in wild-type, and, frequently, regions displaying spontaneous cell death are observed. The cloning of the CPR5 gene revealed a novel putative transmembrane protein with a cytosolic domain containing a nuclear-targeting sequence. The dual role of CPR5 in cell proliferation and cell death control suggests a regulatory link between these two processes.

Apoptosis↗
PubMed2001

Muscarinic receptors control K+ secretion in inner ear strial marginal cells.

K+ secretion in strial marginal cells (SMC) of stria vascularis (SV) is stimulated by beta1-adrenergic receptors. The aim of the present study was to determine, whether SMC from the gerbil inner ear contain muscarinic receptors that inhibit K+ secretion. Receptors were identified with pharmacological tools in functional studies where K+ secretion was monitored as transepithelial current (Isc). The cytosolic Ca2+ concentration ([Ca2+]i) was measured as fluo-4 fluorescence and cAMP production with a colorimetric immunoassay. Further, receptors were identified in SV as transcripts by cloning and sequencing of reverse-transcriptase polymerase chain reaction (RT-PCR) products. The cholinergic receptor agonist carbachol (CCh) caused a transient increase in [Ca2+]i with a half-maximal concentration value (EC50) of (5 +/- 6) x 10(-6) m (n = 29) and a decrease in basal and stimulated cAMP production. Apical CCh had no effect on Isc but basolateral CCh caused a transient increase in Isc with an EC50 of (3 +/- 1) x 10(-6) m and a sustained decrease of Isc with an EC50 of (1.2 +/- 0.2) x 10(-5) m (n = 129). The effects of CCh on Isc and [Ca2+]i were inhibited in the presence of muscarinic antagonist 10(-6) m atropine. Further, the muscarinic antagonists pirenzipine, methoctramine and para-fluoro-hexahydo-sila-defenidol (pFHHSiD) inhibited the CCh-induced transient increase of Isc with affinity constants (KDB) of 3 x 10(-8) m (pKDB = 7.54 +/- 0.19, n = 17), 2 x 10(-6) m (pKDB = 5.71 +/- 0.26, n = 19) and 2 x 10(-8) m (pKDB = 7.65 +/- 0.28, n = 19) and the sustained decrease of Isc with KDB of 7 x 10(-8) m (pKDB = 7.05 +/- 0.09, n = 33), 6 x 10(-6) m (pKDB = 5.21 +/- 0.13, n = 23), 5 x 10(-8) m (pKDB = 7.34 +/- 0.13, n = 31), respectively. RT-PCR of total RNA isolated from SV using primers specific for the M1-M5 muscarinic receptors revealed products of the predicted sizes for the M3- and M4- but not the M1-, M2- and M5-muscarinic receptor subtypes. Sequence analysis confirmed that amplified cDNA fragments encoded gene-specific nucleotide sequences. These results suggest that K+ secretion in SMC is under the control of M3- and M4-muscarinic receptors that may be located in the basolateral membrane of strial marginal cells.

Adrenergic beta-Agonists↗
PubMed2001

Transient evoked and distortion product otoacoustic emissions following successful stapes surgery.

BACKGROUND: The effect of stapes surgery on the recording of otoacoustic emissions is unknown. The aim of the present study was to evaluate the success of stapes surgery by using acoustically evoked otoacoustic emissions as an objective and fast method for postoperative hearing evaluation. METHODS: Transient evoked (TEOAE) and distortion product otoacoustic emissions (DPOAE) were measured consecutively in otosclerosis patients before as well as 3 and 6 months after stapes surgery. RESULTS: Air-bone gaps in the pure-tone audiograms were significantly reduced in all patients. TEOAEs and DPOAEs were not measurable preoperatively and were only evident in one patient postoperatively with low amplitudes in a narrow frequency range. CONCLUSIONS: Despite a subjective hearing improvement and a significant reduction of the conductive loss, otoacoustic emissions are only rarely evident after successful stapes surgery.

Acoustic Impedance Tests↗
PubMed2001

Far-field responses to stimulation of the cochlear nucleus by microsurgically placed penetrating and surface electrodes in the cat.

OBJECT: A new generation of penetrating electrodes for auditory brainstem implants is on the verge of being introduced into clinical practice. This study was designed to compare electrically evoked auditory brainstem responses (EABRs) to stimulation of the cochlear nucleus (CN) by microsurgically implanted surface electrodes and insertion electrodes (INSELs) with stimulation areas of identical size. METHODS: Via a lateral suboccipital approach, arrays of surface and penetrating microelectrodes with geometric stimulation areas measuring 4,417 microm2 (diameter 75 microm) were placed over and inserted into the CN in 10 adult cats. After recording the auditory brainstem response (ABR) at the mastoid process, the CN, and the level of the inferior colliculus, EABRs to stimulation of the CN were recorded using biphasic, charge-balanced stimuli with phase durations of 80 microsec, 160 microsec, and 240 microsec at a repetition rate of 22.3 Hz. Waveform, threshold, maximum amplitude, and the dynamic range of the responses were compared for surface and penetrating electrodes. The EABR waveforms that appeared for both types of stimulation resembled each other closely. The mean impedance was slightly lower (30 +/- 3.4 kohm compared with 31.7 +/- 4.5 kohm, at 10 kHz), but the mean EABR threshold was significantly higher (51.8 microA compared with 40.5 microA, t = 3.5, p = 0.002) for surface electrode arrays as opposed to penetrating electrode arrays. Due to lower saturation levels of the INSEL array, dynamic ranges were almost identical between the two types of stimulation. Sectioning of the eighth cranial nerve did not abolish EABRs. CONCLUSIONS: Microsurgical insertion of electrodes into the CN complex may be guided and monitored using techniques similar to those applied for implantation of surface electrodes. Lower thresholds and almost equivalent dynamic ranges indicate that a more direct access to secondary auditory neurons is achieved using penetrating electrodes.

Animals↗
PubMed2000

Visual system labeled by c-Fos immunohistochemistry after light exposure in the 'blind' subterranean zambian mole-rat (Cryptomys anselli).

The Zambian mole-rat (Cryptomys anselli) is a rodent that lives and forages underground, and under natural conditions is rarely, if ever, exposed to light. Its eye is organized as in other rodents and is prominent but minuscule. The animals do not seem to react to light behaviorally or to orient visually, although exact physiological and/or behavioral experiments have not been conducted to date. Nuclear expression of transcriptional regulatory protein (c-Fos) as a marker of cell activity was studied immunohistochemically in five mole-rats exposed to bright light for 1 h after 3 days in constant darkness, and in four non-stimulated control animals that were kept in darkness for three days and then killed under deep anesthesia. The retinae and retino-recipient areas of non-stimulated animals remained unlabeled, but many of these structures showed strong c-Fos expression bilaterally [retina, dorsal lateral geniculate body (DLG), olivary pretectal nucleus, retrosplenial cortex, neocortex] in light-exposed animals. In contrast, the suprachiasmatic nucleus did not seem to be affected by light stimuli during the experiment. In both light-stimulated and control animals the rudimentary superior colliculus exhibited slight immunoreactivity. Interestingly, the olivary pretectal nucleus, which in mammals is involved in light/dark discrimination, as well as the DLG as part of the image-forming visual system were consistently labeled by c-Fos after light stimulation, indicating that vision in Cryptomys possibly plays a more significant role than previously assumed.

Animals↗
PubMed1999

Trichome cell growth in Arabidopsis thaliana can be derepressed by mutations in at least five genes.

Leaf trichomes in Arabidopsis are unicellular epidermal hairs with a branched morphology. They undergo successive endoreduplication rounds early during cell morphogenesis. Mutations affecting trichome nuclear DNA content, such as triptychon or glabra3, alter trichome branching. We isolated new mutants with supernumerary trichome branches, which fall into three unlinked complementation groups: KAKTUS and the novel loci, POLYCHOME and RASTAFARI. They map to chromosomes IV, II, and V, respectively. The trichomes of these mutants presented an increased DNA content, although to a variable extent. The spindly-5 mutant, which displays a constitutive gibberellin response, also produces overbranched trichomes containing more nuclear DNA. We analyzed genetic interactions using double mutants and propose that two independent pathways, defined by SPINDLY and TRIPTYCHON, act to limit trichome growth. KAKTUS and POLYCHOME might have redundant actions mediating gibberellin control via SPINDLY. The overall leaf polysomaty was not notably affected by these mutations, suggesting that they affect the control of DNA synthesis in a tissue- or cell type-specific manner. Wild-type tetraploids also produce overbranched trichomes; they displayed a shifted polysomaty in trichomes and in the whole leaf, suggesting a developmental program controlling DNA increases via the counting of endoreduplication rounds.

Alleles↗
PubMed1998

[Hyperlipidemia in children and adolescents: diagnosis and therapy].

Severe hyperlipidemias should be diagnosed and treated even in childhood and adolescence, because vascular lipid deposition in the form of fatty streaks and progressive atherosclerotic lesions start to develop early in life. The heterozygous form of familial hypercholesterolemia found in about 1 of 500 newborn infants, and polygenic forms of hypercholesterolemia, are the most frequent forms of primary genetic hypercholesterolemia found in children. Secondary hyperlipidemias, e.g. in diabetes mellitus, hypothyroidism and renal disease, are relatively frequent in children and adolescents and need to be searched for in the diagnostic evaluation, because they can be influenced by treatment of the underlying disorder. Children and adolescents with severe forms of hyperlipidemias should be diagnosed and treated early in life. Dietary modification is the basis of treatment of affected children and can lower LDL cholesterol by about 15-20%. In patients with severe hypercholesterolemia, dietary cholesterol intake should not exceed 150 mg/day in children or 250-300 mg/day in adolescents. Even more important is a reduction of the intake of saturated fats and trans fatty acids and their replacement by polyunsaturated and particularly monounsaturated fats. Some additional lowering of LDL cholesterol may be achieved by the preferential use of vegetable over animal proteins and of complex carbohydrates over sugars. Repeated motivation, counseling and intensive practical training of the patient and family, supported by appropriate teaching materials, are essential for effective dietary treatment. Additional drug treatment is considered in children from the age of 8-9 years of age onwards if, in spite of adequate dietary modification, LDL cholesterol remains above 190 mg/dl (4.9 mmol/l), or above 160 mg/dl (3.9 mmol/l) in the presence of additional risk factors. The drugs of first choice are anion exchange resins (colestyramine or colestipol) because of their well documented efficacy and safety. More convenient to take but often somewhat less effective is beta-sitosterol. If efficacy or compliance with resins or sitosterin is unsatisfactory, fibrates (e.g. bezafibrate, fenofibrate) may be considered as a drug of second choice. Cholesterol synthesis inhibitors are not recommended for general use in children at this time.

Adolescent↗
PubMed1998

Expression patterns of GASA genes in Arabidopsis thaliana: the GASA4 gene is up-regulated by gibberellins in meristematic regions.

The GASA gene family previously identified in Arabidopsis belongs to a wide-spread class of genes found in mono- and dicotyledonous plants, all structurally related to the original GA-regulated GAST1 gene from tomato. They encode small peptides (97 to 112 residues) of unknown function sharing a 60 amino acid conserved C-terminal domain comprising twelve conserved cysteine residues which define a pattern not related to other known cysteine-rich motifs. Northern blot hybridization analysis revealed sequential expression of three genes during flowering, silique development and seed germination. GASA4 transcripts were detected in flower buds. GASA1 transcripts markedly accumulated in siliques, about five days after pollination, and correlated with the peak of GA biosynthesis at this stage of silique development. GASA3 transcripts accumulated at the end of the maturation stage of the silique, and transcripts were still present in dry seeds but degraded rapidly during imbibition. In addition, the GASA4 gene was again actively transcribed after germination and this expression was shown to be dependent on the presence of GAs in GA-deficient mutants. Immunoblot analysis confirmed the presence of the GASA4 gene product in flower buds, seedlings and roots. We focused on the GASA4 gene and characterized its expression. The upstream region (-890 to +128) was fused to the GUS reporter gene. GASA4/GUS expression was detected in transgenic Arabidopsis primarily in all meristematic regions, including vegetative, inflorescence and floral meristems, as well as primary and lateral root tips. In a GA-deficient background (ga1-3), GUS activity in the vegetative meristem was detected only in the presence of supplied GA. In root and flower meristems, basal GUS activity was slightly enhanced by exogenous GA. Interestingly, GA strongly inhibit GUS activity in expanding cotyledons and leaves in ga1-3 mutants supplied with exogenous GAs, as well as in the wild type. The GA-dependent meristem-specific expression pattern suggests that the GASA4 protein plays a role in dividing cells rather than in elongating cells.

Amino Acid Sequence↗
PubMed1998

Clinical phase II evaluation of paclitaxel in combination with cisplatin in metastatic or recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: Paclitaxel as single agent has shown marked activity in several malignancies. The aim of the present phase II trial was to determine the activity of paclitaxel/cisplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: 200 mg/m2 paclitaxel was administered over three hours followed by cisplatin (100 mg/m2), repeated every 22 days. Twenty-eight patients were entered and received a total of 99 cycles (median 2, range 1-6). All patients were evaluable for toxicity, and 25 for response. RESULTS: Hematologic toxicities included leukopenia CTC grade 3 in 13 patients, and grade 4 in five patients, neutropenia grade 3 in nine patients, and grade 4 in eight patients, grade 3 anemia and grade 2 thrombocytopenia in one patient each. Non-hematologic toxicities included hypotension grade 2 (six patients), grade 3 (four patients), and grade 4 (two patients). A decline in renal function was observed in 15 courses and 10 patients, leading to a median delay of 2.5 days. Neurosensory and neuromotor toxicity grade 1 were observed in 13 patients (grade 2: 12 patients; grade 3: one patient), myalgia grade 3 in one patient, asthenia grade 3 in two and grade 4 in one patient. Partial responses were observed in 12 patients for an overall response rate of 48% (95% CI: 28%-68%) with a median response duration of 6.5 months (range 1-10 months). Stable disease was observed in seven patients, of who two also had clinical benefit. CONCLUSIONS: Paclitaxel 200 mg/m2 administered over three hours combined with cisplatin 100 mg/m2 is an active regimen warranting further evaluation.

Adult↗
PubMed1998

Gibberellins promote trichome formation by Up-regulating GLABROUS1 in arabidopsis

Trichome development is dependent on gibberellin (GA) signaling in Arabidopsis thaliana. Using the GA-deficient mutant ga1-3, the GA-response mutant spy-5, and uniconazol (a GA-biosynthesis inhibitor), we show that the GA level response correlates positively with both trichome number and trichome branch number. Two genes, GL1 and TTG, are required for trichome initiation. In ga1-3, coexpression of GL1 and R, the maize TTG functional homolog, under control of the constitutive 35S promoter, restored trichome development, whereas overexpression of neither GL1 nor R alone was sufficient to significantly suppress the glabrous phenotype. We next focused on GL1 regulation by GAs. In the double mutant the gl1-1 glabrous phenotype is epistatic to the spy-5 phenotype, suggesting that GL1 acts downstream of the GA signal transduction pathway. The activity of a beta-glucuronidase reporter gene driven by the GL1 promoter was decreased in the wild type grown on uniconazol and showed a clear GA-dependent activation in ga1-3. Finally, quantification of GL1 transcript levels by reverse transcriptase-polymerase chain reaction demonstrated that relative to wild type, ga1-3 plants contained less transcript. These data support the hypothesis that GAs induce trichome development through up-regulation of GL1 and possibly TTG genes.

Journal Article↗
PubMed1997

[Injuries of the facial skull. First aid and possibilities for reconstruction].

Trauma of the facial skeleton often occurs together with other injuries. Treatment of these patients demand cooperation of all surgical disciplines in order to ensure operative treatment in only a few steps. In all facial injury, fractures of the facial skeleton must be excluded. In clinical examination, occlusion of the teeth is a very important symptom, diagnosis is established by radiology. It is the aim of the treatment to restore the facial skeleton in a good occlusion and position of the bones. It is necessary to restore the function of the stomatognatic system, of the paranasal sinuses and of the eyes. The use of modern osteosynthesis enables the restoration of the original dimensions of the face, i.e. profile, width and height of the face and occlusion of the teeth. Functional disorders like diplopia, perturbation of nasal breathing and of opening of the mouth are avoidable. Different systems of osteosynthesis plates are offered to stabilize the fractured bone, in most cases. Intermaxillary blockage is only necessary during surgery.

Facial Injuries↗
PubMed1996

[Neurologic examinations for facial nerve damage in surgically treated mandibular collum fractures].

Transcranial magnetic stimulation is a new method for objective evaluation of the facial nerve without constraints for the patient. By the first time, especially cortical lesions can be detected objectively. Using this method, a permanent disturbance of the ramus marginalis mandibularis after operative treatment of fractures of the mandibular condyle could be certainly excluded. Therefore, because of the clear presentation and the possibility of enlargement, the deep submandibular approach, using a correct operative technique, can be strictly recommended.

Electromagnetic Fields↗
PubMed1995

GASA, a gibberellin-regulated gene family from Arabidopsis thaliana related to the tomato GAST1 gene.

A multiple gene family of at least four members, related to a GA-stimulated transcript (GAST1) from tomato, was characterized in Arabidopsis thaliana by analysing four related cDNAs, named GASA1 to GASA4. The corresponding peptides display comparable structural features: (1) a putative signal peptide of 18 to 23 residues; (2) a highly divergent hydrophilic region of about 22 amino acids; (3) a conservative 60 amino acid C-terminal domain containing 12 cysteines. This organization has also bean shown in two related peptides from tomato, GAST1 found in shoots and RSI-1 found in early lateral roots. Southern blot hybridization patterns showed single-copy genes for all four members of the GASA family. Accumulation of the various transcripts, monitored by northern blot hybridization, indicated that the various genes are expressed differentially in plant organs: Specific mRNAs were mostly detected in flower buds and immature siliques in the case of GASA1, in siliques and dry seeds in the case of GASA2 and 3, and in growing roots and flower buds in the case of GASA4. At least two of the GASA genes are activated in GA-deficient mutant ga5, as early as 4 to 8 h after spraying with 50 microM GA3. The complex patterns of expression and regulation of the various genes suggest that the related peptides are involved in a developmental regulation process in Arabidopsis.

Amino Acid Sequence↗
PubMed1995

Actin filament organization in the fish keratocyte lamellipodium.

From recent studies of locomoting fish keratocytes it was proposed that the dynamic turnover of actin filaments takes place by a nucleation-release mechanism, which predicts the existence of short (less than 0.5 microns) filaments throughout the lamellipodium (Theriot, J. A., and T. J. Mitchison. 1991. Nature (Lond.). 352:126-131). We have tested this model by investigating the structure of whole mount keratocyte cytoskeletons in the electron microscope and phalloidin-labeled cells, after various fixations, in the light microscope. Micrographs of negatively stained keratocyte cytoskeletons produced by Triton extraction showed that the actin filaments of the lamellipodium are organized to a first approximation in a two-dimensional orthogonal network with the filaments subtending an angle of around 45 degrees to the cell front. Actin filament fringes grown onto the front edge of keratocyte cytoskeletons by the addition of exogenous actin showed a uniform polarity when decorated with myosin subfragment-1, consistent with the fast growing ends of the actin filaments abutting the anterior edge. A steady drop in filament density was observed from the mid-region of the lamellipodium to the perinuclear zone and in images of the more posterior regions of lower filament density many of the actin filaments could be seen to be at least several microns in length. Quantitative analysis of the intensity distribution of fluorescent phalloidin staining across the lamellipodium revealed that the gradient of filament density as well as the absolute content of F-actin was dependent on the fixation method. In cells first fixed and then extracted with Triton, a steep gradient of phalloidin staining was observed from the front to the rear of the lamellipodium. With the protocol required to obtain the electron microscope images, namely Triton extraction followed by fixation, phalloidin staining was, significantly and preferentially reduced in the anterior part of the lamellipodium. This resulted in a lower gradient of filament density, consistent with that seen in the electron microscope, and indicated a loss of around 45% of the filamentous actin during Triton extraction. We conclude, first that the filament organization and length distribution does not support a nucleation release model, but is more consistent with a treadmilling-type mechanism of locomotion featuring actin filaments of graded length. Second, we suggest that two layers of filaments make up the lamellipodium; a lower, stabilized layer associated with the ventral membrane and an upper layer associated with the dorsal membrane that is composed of filaments of a shorter range of lengths than the lower layer and which is mainly lost in Triton.

Actins↗