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Biomedical subjects

M Fink

Publications and source records attributed to M Fink.

At least 91 records · Page 5Linked to original sources
PubMed1999

Electroconvulsive therapy and mental retardation.

Reports on use of electroconvulsive therapy (ECT) in persons with mental retardation (MR) and mental illness are meager. We describe the successful use of ECT in the management of medication-resistant mental illness in persons with mental retardation. Details of the treatment of five patients with MR and psychotic disorders are reported. ECT was successful after the failure of adequate trials of traditional pharmacotherapy. Persons with MR did not have disproportionate adverse effects of ECT as a consequence of the MR. Four of the five cases reported received maintenance ECT. ECT should be considered in the affective and psychotic disorders occurring in persons with MR when traditional pharmacotherapy fails.

Adolescent↗
PubMed1998

Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney.

A complementary DNA encoding a novel K+ channel, called TASK-2, was isolated from human kidney and its gene was mapped to chromosome 6p21. TASK-2 has a low sequence similarity to other two pore domain K+ channels, such as TWIK-1, TREK-1, TASK-1, and TRAAK (18-22% of amino acid identity), but a similar topology consisting of four potential membrane-spanning domains. In transfected cells, TASK-2 produces noninactivating, outwardly rectifying K+ currents with activation potential thresholds that closely follow the K+ equilibrium potential. As for the related TASK-1 and TRAAK channels, the outward rectification is lost at high external K+ concentration. The conductance of TASK-2 was estimated to be 14.5 picosiemens in physiological conditions and 59.9 picosiemens in symmetrical conditions with 155 mM K+. TASK-2 currents are blocked by quinine (IC50 = 22 microM) and quinidine (65% of inhibition at 100 microM) but not by the other classical K+ channel blockers tetraethylammonium, 4-aminopyridine, and Cs+. They are only slightly sensitive to Ba2+, with less than 17% of inhibition at 1 mM. As TASK-1, TASK-2 is highly sensitive to external pH in the physiological range. 10% of the maximum current was recorded at pH 6. 5 and 90% at pH 8.8. Unlike all other cloned channels with two pore-forming domains, TASK-2 is essentially absent in the brain. In human and mouse, TASK-2 is mainly expressed in the kidney, where in situ hybridization shows that it is localized in cortical distal tubules and collecting ducts. This localization, as well as its functional properties, suggest that TASK-2 could play an important role in renal K+ transport.

Amino Acid Sequence↗
PubMed1998

A mammalian two pore domain mechano-gated S-like K+ channel.

Aplysia S-type K+ channels of sensory neurons play a dominant role in presynaptic facilitation and behavioural sensitization. They are closed by serotonin via cAMP-dependent phosphorylation, whereas they are opened by arachidonic acid, volatile general anaesthetics and mechanical stimulation. We have identified a cloned mammalian two P domain K+ channel sharing the properties of the S channel. In addition, the recombinant channel is opened by lipid bilayer amphipathic crenators, while it is closed by cup-formers. The cytoplasmic C-terminus contains a charged region critical for chemical and mechanical activation, as well as a phosphorylation site required for cAMP inhibition.

Amino Acid Sequence↗
PubMed1998

A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids.

TWIK-1, TREK-1 and TASK K+ channels comprise a class of pore-forming subunits with four membrane-spanning segments and two P domains. Here we report the cloning of TRAAK, a 398 amino acid protein which is a new member of this mammalian class of K+ channels. Unlike TWIK-1, TREK-1 and TASK which are widely distributed in many different mouse tissues, TRAAK is present exclusively in brain, spinal cord and retina. Expression of TRAAK in Xenopus oocytes and COS cells induces instantaneous and non-inactivating currents that are not gated by voltage. These currents are only partially inhibited by Ba2+ at high concentrations and are insensitive to the other classical K+ channel blockers tetraethylammonium, 4-aminopyridine and Cs+. A particularly salient feature of TRAAK is that they can be stimulated by arachidonic acid (AA) and other unsaturated fatty acids but not by saturated fatty acids. These channels probably correspond to the functional class of fatty acid-stimulated K+ currents that recently were identified in native neuronal cells but have not yet been cloned. These TRAAK channels might be essential in normal physiological processes in which AA is known to play an important role, such as synaptic transmission, and also in pathophysiological processes such as brain ischemia. TRAAK channels are stimulated by the neuroprotective drug riluzole.

Amino Acid Sequence↗
PubMed1998

ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals.

BACKGROUND: Presence of the D allele or homozygosity for the deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In 2267 male Caucasians the relation of the ACE I/D gene polymorphism to CAD and MI were investigated. An association of the D allele to CAD was detected in younger subjects (e.g. < 61.7 years, mean value), but not in older patients (e.g. > or = 61.7 years). Additional exclusion of individuals with other cardiovascular risk factors (e.g. high BMI) produced an even stronger association of the D allele to CAD. In contrast, a relation of this polymorphism to non-fatal MI was only observed in older subjects; additional limitation to individuals without cardiovascular risk factors (e.g. BMI and/or diabetes) yielded a further enhancement of this association to MI. In younger subjects (e.g. < 61.7 years) the gene polymorphism was not related to non-fatal MI even after exclusion of additional risk factors. CONCLUSIONS: The present large case-control study strengthens the assumption of an association of the ACE D allele with the risk of ischemic heart disease.

Adult↗
PubMed1998

Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction.

The Del allele of the apolipoprotein B (apoB) signal peptide (SP) insertion/deletion (Ins/Del) polymorphism has been shown to be associated with elevated plasma levels of apoB, cholesterol and low density lipoprotein. It was the aim of the present study to analyse the relation of this gene variation to the risk of coronary artery disease (CAD) and of myocardial infarction (MI) in a population of 2259 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. ApoB SP DelDel genotypes had significantly higher apoB plasma concentrations than InsIns homozygotes (P = 0.0001) and InsDel heterozygotes (P = 0.002); however, the apoB plasma levels of InsIns and InsDel genotypes were essentially the same (P = 0.54). Similar observations were made with respect to ApoB SP genotype-dependent cholesterol plasma concentrations. Since the apoB plasma level was not only associated with the apoB SP Ins/Del gene variation but also to the extent of coronary artery disease (P <0.0001), individuals with an InsIns genotype and without CAD had the lowest and subjects with a DelDel genotype and triple vessel disease the highest apoB plasma levels (P <0.0001). An association of the apoB SP Ins/Del gene variation with CAD was not detected, neither in the total population nor in low risk groups. In contrast, the gene variation was associated with MI (P <0.05). An Odds ratio of 1.18 (95% CI, 1.01-1.39) associated with the Del allele was detected in the total sample (P <0.02). In a subpopulation of individuals with low plasma triglyceride levels ( <154 mg/dl; mean value) and an DD genotype of the angiotensin I-converting enzyme insertion/deletion gene polymorphism an Odds ratio of 2.01 (1.42-3.05) was calculated (P <0.001). The present study presents evidence for a statistically significant difference in the development of MI between genotype classes of the apoB SP Ins/Del gene polymorphism.

Alleles↗
PubMed1998

Focusing and steering through absorbing and aberrating layers: application to ultrasonic propagation through the skull.

The time-reversal process is applied to focus pulsed ultrasonic waves through the human skull bone. The aim here is to treat brain tumors, which are difficult to reach with classical surgery means. Such a surgical application requires precise control of the size and location of the therapeutic focal beam. The severe ultrasonic attenuation in the skull reduces the efficiency of the time reversal process. Nevertheless, an improvement of the time reversal process in absorbing media has been investigated and applied to the focusing through the skull [J.-L. Thomas and M. Fink, IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43, 1122-1129 (1996)]. Here an extension of this technique is presented in order to focus on a set of points surrounding an initial artificial source implanted in the tissue volume to treat. From the knowledge of the Green's function matched to this initial source location a new Green's function matched to various points of interest is deduced in order to treat the whole volume. In a homogeneous medium, conventional steering consists of tilting the wave front focused on the acoustical source. In a heterogeneous medium, this process is only valid for small angles or when aberrations are located in a layer close to the array. It is shown here how to extend this method to aberrating and absorbing layers, like the skull bone, located at any distance from the array of transducers.

Brain Neoplasms↗
PubMed1998

Deploying a new model for clinical information delivery.

Information is a dynamic, potentially high-value resource that institutions can use to achieve superior performance. The myriad of advanced information technology projects, however, delivers to the institution's clinical and business processes unpredictable deluges of information objects, both paper and electronic, that may add little value to the processes. Also, because the information arrival is often a trigger for work steps, its illogical arrival may actually dilute productivity and quality. The article describes an information distribution engine in use at a large hospital in the southwestern United States that allows remotely located recipients to define individualized rules for controlling the subset of diverse information that they receive, select its transmission and display media, and choreograph the sequence and timing of its arrival at their desktops.

Attitude to Computers↗
PubMed1997

TASK, a human background K+ channel to sense external pH variations near physiological pH.

TASK is a new member of the recently recognized TWIK K+ channel family. This 395 amino acid polypeptide has four transmembrane segments and two P domains. In adult human, TASK transcripts are found in pancreas<placenta<brain<lung, prostate<heart, kidney<uterus, small intestine and colon. Electrophysiological properties of TASK were determined after expression in Xenopus oocytes and COS cells. TASK currents are K+-selective, instantaneous and non-inactivating. They show an outward rectification when external [K+] is low ([K+]out = 2 mM) which is not observed for high [K+]out (98 mM). The rectification can be approximated by the Goldman-Hodgkin-Katz current equation that predicts a curvature of the current-voltage plot in asymmetric K+ conditions. This strongly suggests that TASK lacks intrinsic voltage sensitivity. The absence of activation and inactivation kinetics as well as voltage independence are characteristic of conductances referred to as leak or background conductances. For this reason, TASK is designated as a background K+ channel. TASK is very sensitive to variations of extracellular pH in a narrow physiological range; as much as 90% of the maximum current is recorded at pH 7.7 and only 10% at pH 6.7. This property is probably essential for its physiological function, and suggests that small pH variations may serve a communication role in the nervous system.

Amino Acid Sequence↗
PubMed1997

The structure, function and distribution of the mouse TWIK-1 K+ channel.

The two P domain K+ channel mTWIK-1 has been cloned from mouse brain. In Xenopus oocytes, mTWIK-1 currents are K+-selective, instantaneous, and weakly inward rectifying. These currents are blocked by Ba2+ and quinine, decreased by protein kinase C and increased by internal acidification. The apparent molecular weight of mTWIK-1 in brain is 81 kDa. A 40 kDa form is revealed after treatment with a reducing agent, strongly suggesting that native mTWIK-1 subunits dimerize via a disulfide bridge. TWIK-1 mRNA is expressed abundantly in brain and at lower levels in lung, kidney, and skeletal muscle. In situ hybridization shows that mTWIK-1 expression is restricted to a few brain regions, with the highest levels in cerebellar granule cells, brainstem, hippocampus and cerebral cortex.

Amino Acid Sequence↗
PubMed1997

[Recent developments in lacrimal duct endoscopy].

BACKGROUND: At the moment digital dacryocystography yields the most exact results in lacrimal diagnostics. The main disadvantage lies in the dependency of high tech X-ray systems and an angiography unit, which raise enormously the costs of the examination. Recently a new diagnostic system of the lacrimal pathway is available. PATIENTS AND METHODS: Miniaturizing of endoscopes and new developments in the fiberoptic technology made it possible to introduce these mini-endoscopes into the canaliculi and perform antegrade examination of canaliculi, lacrimal sac and ductus nasolacrimalis. 86 patients agreed to this examination. With this examination a direct visualisation of the mucous membrane of the lacrimal pathways and possible pathological alterations were possible. RESULTS: In case of axial illumination and syringing of the lacrimal system good visibility can be achieved and an exact examination is possible. Especially for endoscopy modified probes of Bangerter provide an exact examination at narrow areas and areas of bendings too. Different reasons for stenosis of the lacrimal pathways could be identified, especially 2 cases of a lacrimal sac tumor. CONCLUSIONS: The use of this new miniendoscope provides a very good examination under direct visualisation of the lacrimal pathway independent of a high tech X-ray equipment. The goal is to use this new endoscope on the one hand only for diagnostic reasons as endoscope and on the other hand in combination with a laser fiber to perform an antegrade laser dacryocystorhinostomy.

Adolescent↗