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Biomedical subjects

S Clemens

Publications and source records attributed to S Clemens.

At least 19 recordsLinked to original sources

Toxic metal accumulation, responses to exposure and mechanisms of tolerance in plants.

Over the past 200 years emissions of toxic heavy metals have risen tremendously and significantly exceed those from natural sources for practically all metals. Uptake and accumulation by crop plants represents the main entry pathway for potentially health-threatening toxic metals into human and animal food. Of major concern are the metalloids arsenic (As) and selenium (Se), and the metals cadmium (Cd), mercury (Hg), and lead (Pb). This review discusses the molecular mechanisms of toxic metal accumulation in plants and algae, the responses to metal exposure, as well as our understanding of metal tolerance and its evolution. The main emphasis will be on cadmium, which is by far the most widely studied of the non-essential toxic metals/metalloids. Entry via Zn2+, Fe2+, and Ca2+ transporters is the molecular basis of Cd2+ uptake into plant cells. Much less is known about the partitioning of non-essential metals and about the genes underlying the enormous diversity among plants with respect to Cd accumulation in different tissues. Numerous studies have described symptoms and responses of plants upon toxic metal exposure. Mysterious are primary targets of toxicity, the degree of specificity of responses, the sensing and the signaling events that lead to transcriptional activation. All plants apparently possess a basal tolerance of toxic non-essential metals. For Cd and As, this is largely dependent on the phytochelatin pathway. Not understood is the molecular biology of Cd hypertolerance in certain plant species such as the metallophytes Arabidopsis halleri or Thlaspi caerulescens.

Drug Tolerance↗

[Optical lamellar-penetrating keratoplasty with stem cell transplantation in high-risk cases].

BACKGROUND: Stem cells of the corneal epithelium are located mainly at the sclerocorneal limbus, and are essential for the maintenance of a healthy corneal surface. Limbal stem cell deficiency leads--depending on intensity and extension--to several corneal alterations. The appearance of limbal stem cell deficiency is chiefly concentrated on pemphigoids, Herpes relapses and alkali burns and represents the main part of high-risk keratoplasty. The different types of limbal stem cell deficiency (partial or total) are usually treated with several surgical techniques. Total limbal deficiency can be treated with limbal transplantation, either of the healthy eye (limbal autograft), or using material of another donor (limbal allograft). METHODS AND RESULTS: Lamellar-penetrating keratoplasty (L-P-KP) has been carried out in five patients. Unlike recent surgical techniques containing ring-shaped or circular transplantations, a stripe-like lamellar preparation was performed. L-P-KP involves a peripheral lamellar and a central penetrating keratoplasty combined with limbal stem cell transplantation. In four of six cases, the transplant has been successfully kept clear without the occurrence of corneal decompensation or ulceration. No major changes could be seen between pre- and postoperative visual acuity. The mean observation period was 24 months. DISCUSSION: L-P-KP offers a new surgical opportunity in the treatment of high-risk cases of limbal deficiency.

Adolescent↗

[The influence of transport on organ cultured corneas. An experimental study of porcine corneal endothelium].

BACKGROUND: To investigate the influence of transport on the quality of corneas in organ culture, based on the vitality of the corneal endothelium. METHODS: Transport was simulated for 222 porcine corneal disks. These were placed in standard transportation containers filled with organ culture medium II, kept in an incubator and then shaken on a laboratory shaker. RESULTS: Agitated corneas at all acceleration rates always showed less endothelial cell damage than corneas kept motionless. The best condition was found after maximum accelerations of 0.10 g and 0.72 g. Damage consisted predominantly of disseminated cell loss and circular cell damage. A storage temperature of 37 degrees C caused most harm to the endothelium. CONCLUSION: The reduction in endothelial damage found in corneas after agitation can be attributed to a better distribution of nutrients in the transportation container. Assuming transferability, a better quality of human grafts can be achieved by inducing slight motions of corneas in organ culture.

Animals↗

[Application of EMLA creme before upper lid blepharoplasty].

BACKGROUND: The injection of local anesthesia before upper lid blepharoplasty is perceived as unpleasant and painful by some patients. METHODS: In an intraindividual randomized prospective study, 14 patients undergoing upper lid blepharoplasty on both sides were examined. Before the operation the EMLA creme was put on one side. The pain sensibility was checked before and after using EMLA creme and during the infiltration of anesthesia and the operation. RESULTS: The sensitivity before putting on EMLA creme was equal in all patients on both sides. After application there was a distinct difference between the sides. During the infiltration of anesthesia 12 patients reported low and 2 patients medium pain on the treated side, while on the non-treated side 5 patients reported low, 4 patients medium, and 5 patients severe pain. CONCLUSIONS: Applying EMLA creme before an operation reduces the pain sensitivity during infiltration of anesthesia and during the operation.

Administration, Topical↗

Reversal of the circadian expression of tyrosine-hydroxylase but not nitric oxide synthase levels in the spinal cord of dopamine D3 receptor knockout mice.

Circadian rhythms have been described for numerous transmitter synthesizing enzymes in the brain but rarely in spinal cord. We measured spinal tyrosine-hydroxylase (TH) and nitric oxide synthase (NOS) levels in the thoracic intermediolateral nucleus, the location of sympathetic preganglionic neurons, in male wild type (WT) and dopamine D(3) receptor knockout mice (D(3)KO). TH and NOS levels both displayed circadian patterns in WT and D(3)KO animals with overall reduced TH and increased NOS expression in the D(3)KO mice. The circadian pattern of NOS expression was similar in WT and D(3)KO mice. In contrast, TH expression was inverted in D(3)KO mice, with TH levels consistently lower than in WT throughout the day, but strongly increased temporarily 1 h prior to daylight. TH is the rate-limiting enzyme for the production of dopamine. Spinal dopamine dysfunction is implicated in a sleep disorder called restless legs syndrome (RLS). RLS follows a circadian rhythm and is relieved clinically by dopamine D(3) receptor agonists. Our observations of an altered circadian pattern in spinal dopamine synthesis in D(3)KO animals may provide insight into putative dopaminergic mechanisms contributing to RLS.

Animals↗

[Minimally invasive endoscopic surgery of the lacrimal drainage system--two case reports].

BACKGROUND: Dacryoendoscopy is a standard procedure to directly evaluate the lacrimal system. The existence and localisation of dacryostenosis and mucosal changes as well as rare diseases in the drainage system, such as intracanalicular foreign bodies or dacryoliths, can be reliably detected and treated by minimally invasive endoscopic surgery. HISTORY AND SIGNS: A patient treated by canaliclulodacryozystorhinostomy with silicone tube intubation 5 years ago had a long symptom-free period but now shows tearing (epiphora) and occasional mucous secretion. During endoscopy residues of a silicone tube coated with a biofilm could be removed over the lacrimal canaliculus and then tested for microbiological contamination. A second patient with tearing, light mucous secretion and positive nasolacrimal duct irrigation was initially diagnosed with a tear-film disorder. Dacryoendoscopy showed a dacryolith in the saccus lacrimalis. This was consequently fragmented using a microdrill system and fully removed through the nasolacrimal duct as well as the lacrimal canaliculus. CONCLUSIONS: Endoscopy of the proximal and distal lacrimal system allows the assessment of intracanalicular structures and a reliable detection or exclusion of disorders in the draining system. This method is of great diagnostic importance as symptoms are frequently non-specific and the causes are multiple. Through endoscopy in combination with the use of a microdrill system the lacrimal system can be reopened and adequately reconstructed.

Adult↗

The cartilage-sparing versus the cartilage-cutting technique: a retrospective quality control comparison of the Francesconi and Converse otoplasties.

From a total of 281 patients with protruding ears who underwent a bilateral otoplasty between 1990 and 2001, a group of 28 (10%) was selected for a retrospective quality control study. The goal was to compare two methods of otoplasty, the Francesconi, a cartilage-sparing technique, and the Converse, a cartilage-cutting technique, in terms of objectively measurable and subjectively discernable differences in results. Objective parameters included measurement of the three cephaloauricular distances and the conchoscapal angle. An independent plastic surgeon performed the evaluation by means of a systematic evaluation system for rating cosmetic surgical procedures and a 5-point visual analog scale for rating satisfaction. The patients' subjective rate of satisfaction also was investigated using the 5-point scale. The mean medial and inferior cephaloauricular distances were significantly smaller in the Francesconi group. The concoscaphal angle was 90 degrees, or less in all the patients of the Francesconi group, but more than 90 degrees in eight patients (57%) of the Converse group (p = 0.041). Accordingly, the independent surgeon found adequate correction of protrusion in 86% of the Francesconi group and 50% of the Converse group (p = 0.050). His satisfaction rate was significantly in favor of the Francesconi technique (p = 0.006). Not unexpectedly, the patients' satisfaction rate was comparably high in both groups, and there was no statistical difference between them. In conclusion, the quality control led to a clear preference of the Francesconi over the Converse otoplasty. In addition, the assessment of the postoperative results with the systematic evaluation system offered an excellent information base by which to judge the results of otoplasty. Consequent use of this evaluation system will lead to progress in the surgical procedure.

Adolescent↗

[20-MHz ultrasound of pre-saccular lacrimal ducts].

BACKGROUND: In clinical practice, ultrasound examination of the lacrimal drainage system is not able to represent the lacrimal canaliculi with a high quality but the high-resolution ultrasound with 20 MHz transducer is a better possibility to get images of the lacrimal canaliculi. PATIENTS AND METHODS: A total of 20 patients suffering from diseases of the lacrimal drainage system were examined ultrasonographically. Detection and localisation of the lacrimal canaliculi was made by a 20 MHz sector scanner in combination with the ultrasound diagnostic system I. After patient positioning, the high-resolution ultrasound investigation was done via immersion connection (methylcellulose). Instillation of viscoelastic substances (e.g. Healon) was necessary to detect the lacrimal canaliculi. RESULTS: In all investigated patients, the high-resolution ultrasound (transducer frequency of 20 MHz) allowed reproducible images of the lacrimal drainage system. Without viscoelastic substances, a good echographic visualisation of canaliculi structures was obtained from patients with chronic canaliculitis or dislocated punctum plugs. In chronic canaliculitis the ultrasonic images showed an ectatic canaliculus (diverticulum) and high-reflective structures (concrements). CONCLUSION: The high-resolution ultrasound (transducer frequency of 20 MHz) seems to be well suited for investigations of the lacrimal drainage system. In comparison with ultrasound biomicroscopy the resolution is lower but the depth of penetration is higher. The use of 20 MHz ultrasonic examination can be helpful in the clinical diagnostic of chronic canaliculitis.

Chronic Disease↗

A modulatory role for oxygen in shaping rhythmic motor output patterns of neuronal networks.

It is becoming increasingly evident that O(2)-uptake in animal tissue is not only devoted to energy production. Here we review recent findings on a novel role of tissue oxygenation, notably in controlling the operation of neuronal networks in the central nervous system. Electrophysiological recordings in vivo and in vitro from rhythmically-active motor pattern generating networks in the lobster stomatogastric ganglion (STG) have revealed that oxygen is able to act in a manner equivalent to a classical neuromodulator. Local P(O(2)) variations within the low, but physiological range of 1-6 kPa are able to shape ongoing activity of these networks and therefore the motor behaviours in which they are involved. Oxygen's contribution to two of these, feeding and moulting, have been investigated. Importantly, the P(O(2)) effects are not related to hypoxic depression but are highly specific in terms of the network, neuron and even the synapse targeted. Our results are discussed in terms of functional significance and new research directions for mammalian physiology.

Animals↗

Arabidopsis thaliana expresses a second functional phytochelatin synthase.

Phytochelatins represent a major detoxifying pathway for heavy metals in plants and many other organisms. The Arabidopsis thaliana CAD1 (=AtPCS1) gene encodes a phytochelatin synthase and cad1 mutants are phytochelatin deficient and cadmium hypersensitive. The Arabidopsis genome contains a highly homologous gene, AtPCS2, of which expression and function were studied in order to understand the apparent non-redundancy of the two genes. Low constitutive AtPCS2 expression is detected in all plant organs analyzed. The AtPCS2 gene encodes a functional phytochelatin synthase as shown by expression in Saccharomyces cerevisiae and the complementation of a Schizosaccharomyces pombe phytochelatin synthase knockout strain.

Aminoacyltransferases↗

Molecular mechanisms of plant metal tolerance and homeostasis.

Transition metals such as copper are essential for many physiological processes yet can be toxic at elevated levels. Other metals (e.g. lead) are nonessential and potentially highly toxic. Plants--like all other organisms--possess homeostatic mechanisms to maintain the correct concentrations of essential metal ions in different cellular compartments and to minimize the damage from exposure to nonessential metal ions. A regulated network of metal transport, chelation, trafficking and sequestration activities functions to provide the uptake, distribution and detoxification of metal ions. Some of the components of this network have now been identified: a number of uptake transporters have been cloned as well as candidate transporters for the vacuolar sequestration of metals. Chelators and chaperones are known, and evidence for intracellular metal trafficking is emerging. This recent progress in the molecular understanding of plant metal homeostasis and tolerance is reviewed.

ATP-Binding Cassette Transporters↗

Biochemical networks in nervous systems: expanding neuronal information capacity beyond voltage signals.

In addition to synaptically mediated signals that are based on changes in membrane potential, neurons also generate and receive many types of signals that involve biochemical pathways, some of which are independent of voltage. Although networks of biochemical pathways have often been thought of as being only neuromodulatory, recent computational and experimental studies have highlighted how these pathways can also integrate and transfer information themselves. Interactions between biochemical pathways involving positive and negative feedback loops allow biochemical signals to exhibit emergent properties, most notably bistability and oscillations. New and evolving techniques, including real-time imaging of second messengers, hold the promise of illuminating information processing that cannot be detected using microelectrodes, and revealing how 'biochemical integration' might contribute to the computational abilities of the nervous system.

Animals↗

Caenorhabditis elegans expresses a functional phytochelatin synthase.

The formation of phytochelatins, small metal-binding glutathione-derived peptides, is one of the well-studied responses of plants to toxic metal exposure. Phytochelatins have also been detected in some fungi and some marine diatoms. Genes encoding phytochelatin synthases (PCS) have recently been cloned from Arabidopsis, wheat and Schizosaccharomyces pombe. Surprisingly, database searches revealed the presence of a homologous gene in the Caenorhabditis elegans genome, DDBJ/EMBL/GenBank accession no. 266513. Here we show that C. elegans indeed expresses a gene coding for a functional phytochelatin synthase. CePCS complements the Cd2+ sensitivity of a Schizosaccharomyces pombe PCS knock-out strain and confers phytochelatin synthase activity to these cells. Thus, phytochelatins may play a role for metal homeostasis also in certain animals.

Aminoacyltransferases↗

Identified serotonergic neurons in the Tritonia swim CPG activate both ionotropic and metabotropic receptors.

Although G-protein-coupled (metabotropic) receptors are known to modulate the production of motor patterns, evidence from the escape swim central pattern generator (CPG) of the nudibranch mollusk, Tritonia diomedea, suggests that they might also participate in the generation of the motor pattern itself. The dorsal swim interneurons (DSIs), identified serotonergic neurons intrinsic to the Tritonia swim CPG, evoke dual component synaptic potentials onto other CPG neurons and premotor interneurons. Both the fast and slow components were previously shown to be due to serotonin (5-HT) acting at distinct postsynaptic receptors. We find that blocking or facilitating metabotropic receptors in a postsynaptic premotor interneuron differentially affects the fast and slow synaptic responses to DSI stimulation. Blocking G-protein activation by iontophoretically injecting the GDP-analogue guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) did not significantly affect the DSI-evoked fast excitatory postsynaptic potential (EPSP) but decreased the amplitude of the slow component more than 50%. Injection of the GTP analogues guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and 5'-guanylyl-imidodiphosphate, to prolong G-protein activation, had mixed effects on the fast component but increased the amplitude and duration of the slow component of the DSI-evoked response and, with repeated DSI stimulation, led to a persistent depolarization. These results indicate that the fast component of the biphasic synaptic potential evoked by a serotonergic CPG neuron onto premotor interneurons is mediated by ionotropic receptors (5-HT-gated ion channels), whereas the slow component is mediated by G-protein-coupled receptors. A similar synaptic activation of metabotropic receptors might also be found within the CPG itself, where it could exert a direct influence onto motor pattern generation.

Animals↗

Developing tools for phytoremediation: towards a molecular understanding of plant metal tolerance and accumulation.

Certain plant species and genotypes are able to accumulate large quantities of heavy metals in their shoots. Based on this trait the concept of phytoremediation was developed, i.e. the use of metal hyperaccumulating plants for the cleansing of contaminated soils and water. In order to more efficiently use this capacity, an engineering of plants might be needed. However, very little is known about the underlying molecular mechanisms. Our work is focussing on the identification and characterization of plant genes involved in plant metal uptake, tolerance and accumulation. Phytochelatins are small glutathione-derived metal-binding peptides which are part of the plant metal detoxification system. Genes encoding phytochelatin synthases have been cloned and are now being studied with regard to their regulation, biochemistry and biotechnological potential. Another project aimes at the dissection of metal responses in the metallophyte Arabidopsis halleri. This plant, a close relative to the model plant Arabidopsis thaliana, is Cd hypertolerant and Zn hyperaccumulating. It grows, for instance, on medieval mining sites in the Harz mountains in Germany and in many other metal-contaminated sites in Central Europe. We have isolated metal-regulated genes from A. halleri and molecularly analyzed interesting candidate genes with regard to their function and involvement in metal accumulation and tolerance.

Biotechnology↗

Clinical diagnosis of chronic canaliculitis by 20-MHz ultrasound.

The practical value of high-resolution ultrasound (transducer frequency of 20 MHz) in the study of the lacrimal canaliculi has been proven. It can also be used in the clinical diagnosis of chronic canaliculitis. If the classic symptoms are absent, the clinical diagnosis is often inaccurate, and treatment is insufficient. Representative images of normal cases and of chronic canaliculitis illustrate the potential of high-resolution ultrasound. In our patient, 20-MHz scanner images revealed pathological findings which were invisible during slitlamp examination. Ultrasonic images of chronic canaliculitis showed ectasia of the canaliculus and sulfur grains. High-resolution ultrasonic examination of the lacrimal drainage system demonstrated that the 20-MHz scanner used was able to show concrements (sulfur grains), measuring 1-2 mm in diameter. Such more reflective structures (like sulfur grains) are a pathognomonic sign of chronic canaliculitis. Our report confirms the efficiency of 20-MHz sonography in the diagnosis of canaliculitis without any side effects.

Adult↗

Expression of the wax-specific condensing enzyme CUT1 in Arabidopsis.

The Arabidopsis thaliana gene CUT1 encodes a very-long-chain fatty acid-condensing enzyme required for the production of epicuticular wax in bolting stems. We have examined the expression pattern of CUT1 in Arabidopsis at different developmental stages and under different environmental conditions. RNA blot analysis showed that CUT1 was highly expressed in shoots, but not in roots. CUT1 expression was detectable throughout development. Light was required for CUT1 expression, and expression was increased by salt and drought treatments. The promoter region of the CUT1 gene was cloned, and 1.2 kb of the sequence 5' to the translation start codon was used to direct beta-glucuronidase (GUS) expression in transgenic plants. Histochemical and fluorometric (quantitative) GUS assays confirmed that the CUT1 promoter directed epidermal-specific expression and was highly active in Arabidopsis and in tobacco. A construct using the CUT1 promoter to drive CUT1 expression (CUT1p-CUT1) was used to transform Arabidopsis. Transgenic plants which had somewhat increased (overexpression) or greatly reduced (co-suppression) wax loads were recovered. Thus, the CUT1 promoter should be useful for genetic engineering applications that require epidermis-specific expression of genes.

Acyltransferases↗