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Biomedical subjects

C Deutsch

Publications and source records attributed to C Deutsch.

At least 19 recordsLinked to original sources
PubMed1992

Self-tonometry: technical aspects of calibration and clinical application.

Self-tonometry could be established as an important diagnostic tool in the early diagnosis and follow-up of glaucoma provided that a self-tonometer is precise, safe and easy to use. Furthermore, it has to comply with the legal standards for tonometer calibration. A new software-controlled detection system for the self-tonometer permits the evaluation of external factors during the measurement which influence the precision of the tonometric readings. The updated version of the self-tonometer (ST) was compared to the Draeger hand-held applanation tonometer (HAT) in a clinical study with 82 patients (151 eyes). The results show a regression line characterized by a slope of 0.99, an y interception of 1.41, a correlation coefficient of 0.96 and a standard deviation for the ST readings of +/- 1.78 mmHg. Self-tonometry improves the IOP monitoring as well as patient compliance and therefore is a potential diagnostic tool in the management of glaucoma.

Calibration↗
PubMed1992

Gene expression in mental illness: a navigation chart to future progress.

An initial course in disentangling complex causal interactions in psychiatric illnesses, we suggest, is finding co-familial traits with classical Mendelian segregation. Starting with non-Mendelian traits, three methods can be used to find underlying Mendelian phenotypes. (1) Statistically-inferred latent traits, with more nearly Mendelian transmission than the measures from which they are derived, can serve as pointers to concrete Mendelian phenotypes. (2) Linkage of non-Mendelian traits to genetic markers, if it can be established, can be followed by searching for phenotypes that discriminate carriers from non-carriers of the imputed trait gene. (3) In the long run, the most successful method is likely to be direct refinement of non-Mendelian behavioral and physiological traits into more fundamental components.

Bipolar Disorder↗
PubMed1992

Diverse K+ channels in primary human T lymphocytes.

We used patch clamp techniques to identify and characterize a variety of K+ channels in primary human peripheral T lymphocytes. The most common channel observed in cell-attached configuration was voltage gated and inactivating. In ensemble averages, the kinetics of its activation and inactivation were similar to those of the whole-cell, voltage-gated K+ current described previously (Cahalan, M. D., K. G. Chandy, T. E. DeCoursey, and S. Gupta. 1985. J. Physiol. [Lond.]. 358:197-237; Deutsch, C., D. Krause, and S. C. Lee. 1986. J. Physiol. [Lond.]. 372:405-423), suggesting that this channel underlies the major portion of the outward current in lymphocytes. A small fraction of the time, this or another very similar channel was observed to inactivate significantly more slowly. Another channel type observed in cell-attached recording was seen less frequently and was transient in its appearance. This channel has a unitary conductance of approximately 10 pS, similar to the voltage-gated channel, but its voltage-independent gating, lack of inactivation, and different kinetic parameters showed it to be distinct. In whole-cell recording there is often a significant plateau current during sustained depolarization. Experiments using whole-cell and excised outside-out configurations indicate that at least part of this residual current is carried by K+ and, as opposed to the predominant voltage-gated current, is charybdotoxin insensitive. These findings are consistent with evidence that implicates charybdotoxin-sensitive and -insensitive components in T lymphocyte proliferation and volume regulation.

Adult↗
PubMed1992

[2 years self-tonometry. Acceptance and results].

For more than 2 years we have been trying out a microprocessor-controlled self-tonometer to determine its clinical usefulness. Most of the measurements were taken with two instruments (A and B). In vitro calibration series on human donor corneas gave good results over the whole pressure range. In a patient series both instruments were compared with the established hand-held applanation tonometer put out by Draeger (HAT). Each self-tonometer was applied three times, followed by a controlling measurement with the HAT. The correlation coefficient between instrument A and HAT was 0.85 with a standard deviation of +/- 1.9126 mmHg. Instrument B showed a better correlation (r = 0.904), the standard deviation was similar to tonometer A (SD = +/- 1.8598 mmHg). Most of the values obtained by the self-tonometers-about 50%-deviated from the corresponding HAT values by +/- 1 mmHg. The new measurement principle was accepted by 75% of all patients. Improvements in the details are planned in order to simplify tonometer handling and increase the accuracy and precision of the measurements.

Adolescent↗
PubMed1991

Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected.

Using purified human T lymphocytes stimulated in serum-free media with adhered anti-CD3 + exogenous IL-2, we have shown that elevated [cAMP]i (mimicked by CPT-cAMP or induced by the physiological agonist PGE2) directly inhibits mitogen-induced 1) [3H]thymidine incorporation by PBMC, purified T cells, and isolated CD4+ and CD8+ T cell subpopulations; 2) expression of both high- and low-affinity IL-2 receptors; 3) plasma membrane expression of both p55 and p75 subunits of the IL-2 receptor; and 4) expression of p55 mRNA, but not p75 mRNA. The decrease in p55 mRNA is not due to enhanced mRNA metabolism. We conclude that elevated [cAMP]i, acting directly on T cells, inhibits mitogenesis by decreasing IL-2 receptor expression. We discuss the possible physiological relevance for the multiple stages of T cell activation that are sensitive to elevated [cAMP]i.

Binding Sites↗
PubMed1991

Characterization of high affinity binding sites for charybdotoxin in human T lymphocytes. Evidence for association with the voltage-gated K+ channel.

Charybdotoxin (ChTX) inhibits with high affinity a voltage-gated K+ channel that is present in human T lymphocytes. In this system, 125I-ChTX binds specifically and reversibly to a single class of sites which display a Kd of 8-14 pM, as measured by either equilibrium or kinetic binding protocols. The maximum density of sites, 542 sites/cell, correlates well with the density of K+ channel as determined by electrophysiological experiments. Binding of 125I-ChTX is modulated by the ionic strength of the incubation media and by Ca2+. Increasing concentrations of either K+, Na+, or Ca2+ cause inhibition of toxin binding. Inhibition of binding by Ca2+ is due, primarily, to an effect on toxin dissociation rates. Increasing the pH of the external media from 6.8 to 8.5 enhances toxin binding, due to an increase in affinity with no significant effect on the maximum density of receptor sites. Different agents that block the voltage-gated K+ channel in human T lymphocytes, inhibit toxin binding. Mitogen-stimulated T cells display 2.5-3-fold increase in toxin binding as compared with unstimulated control cells. These data, taken together, suggest that 125I-ChTX binding sites identified in this study, represent the predominant voltage-gated K+ channel present in peripheral human T lymphocytes. Therefore, 125I-ChTX is a useful probe for elucidating the physiological role of this type of K+ channel.

Binding Sites↗
PubMed1991

[Clinical and experimental results with a new fully automatic self-tonometer].

In a clinical study 25 patients being treated at the Department of Ophthalmology in the Hamburg University were instructed in self-tonometry using a new automatic tonometer. In a first sequence, three self-measurements were taken by the patients within 1 min; then a control measurement with a motor-driven hand applanation tonometer (HAT) was taken by a physician. The procedure was repeated 6-10 min afterwards without new local anesthesia. In addition, a dynamometer was applied to 5 healthy eyes in order to test the self-tonometer at higher pressure levels. The correlation of repetitive measurements of the self-tonometer showed good results for the patient measurements (r1 = 0.97, SD1 = 1.66 mmHg, r2 = 0.96, SD2 = 1.47 mmHg) and slightly worse values for the measurements with the dynamometer (r3 = 0.97, SD3 = 2.02 mmHg), probably due to the non-physiological deformation of the eye induced by the dynamometer. To establish accuracy, the results were compared to the HAT. The following results were achieved: (r1 = 0.97, s1 = 1.71 mmHg, r2 = 0.96, s2 = 1.49 mmHg, r3 = 0.97, s3 = 2.69 mmHg). Other studies with the self-tonometer will follow in order to optimize its accuracy and design. Self-tonometry under conditions of microgravity is planned for the 2nd German Spacelab Mission and the Russian Space station MIR. In the future, self-tonometry will play an important part in the management of glaucoma.

Animals↗
PubMed1990

Temperature dependence of K(+)-channel properties in human T lymphocytes.

We have used whole-cell patch clamp to determine the temperature dependence of the conductance and gating kinetics of the voltage-gated potassium channel in quiescent, human peripheral blood T lymphocytes. Threshold for activation, steady-state inactivation, and the reversal potential are the same at 22 degrees and 37 degrees C. However, the time-constants for activation, inactivation, deactivation, and release from inactivation are quite sensitive to temperature, changing by at least a factor of five in each case over this range of temperatures. The onset of cumulative inactivation at 22 degrees and 37 degrees C reflects the time-course of deactivation. Peak outward current is approximately twofold greater at 37 degrees C than at 22 degrees C; this increase is also manifest at the single channel level. Energies of activation for conductance, activation, inactivation, deactivation, and release from inactivation are 8.2, 22.1, 25.0, 36.2, and 42.2 kcal/mol, respectively. No new channels were observed at 37 degrees C, and there was no evidence for alteration of the K+ conductance by putative modulators at 22 or 37 degrees C.

Cells, Cultured↗
PubMed1990

[Clinical value of new tonometers].

In a clinical study four different tonometers [a hand-held applanation tonometer (HAT), a tonometer that works according to the principle of Mackay-Marg and two noncontact tonometers (NCT A und NCT B)] were compared with respect to accuracy and precision. In a randomized sequence, two physicians took six measurements of both eyes of 99 patients using the four different instruments. The interval between the two measurements in one eye was 3 min. The correlations of repetitive measurements for one tonometer in one eye showed good results for HAT (r = 0.985, SD = 1.66 mmHg), but significantly worse values for the other three tonometers (Mackay-Marg type: r = 0.85, SD = 3.5 mmHg; NCT A and NCT B: r = 0.91, SD = 2.93 mmHg). To establish the accuracy, the pressure values of the Mackay-Marg type and NCT A and NCT B were compared with those of the well-established HAT. The results were as follows: Mackay-Marg type: r = 0.84, SD = 3.78 mmHg; NCT A: r = 0.86, SD = 4.55 mmHg; NCT B: r = 0.89, SD = 3.26 mmHg). We conclude that the three tonometers tested (one based on the Mackay-Marg principle and the other two on the non-contact principle) are not suitable for clinical and scientific use.

Adolescent↗
PubMed1989

Microprocessor controlled tonometry.

Microprocessors have enabled new techniques to be applied to the design of tonometers. Three new microprocessor controlled tonometers, one operating to the principle of Mackay-Marg (Tono-Pen) and two non-contact airstream tonometers (Pulsair and CT-10) have been examined using as a reference Goldmann and the Hand Held Applanation Tonometers (Draeger-HAT) which used the Goldmann applanation principle. The non-contact tonometers produce a conically formed airstream with top speeds of 90 m/s (CT-10) and 70 m/s (Pulsair) which at the moment of pressure measurement applanates the cornea exactly with a diameter of 4 mm. The readings of the microprocessor controlled tonometers correlate well with the readings of HAT (Tono-Pen r = 0.8414 and s = 3.783, CT-10 r = 0.8606 and s = 4.5477, Pulsair r = 0.8968 and s = 3.2641, where r is the correlation coefficient and s is the standard deviation in mmHg). Repeated measurements with one tonometer give the following standard deviations (HAT 1.6617, Tono-Pen 3.4969, CT-10 2.9179, Pulsair 2.9434). Although the three new instruments are able to measure the intraocular pressure in a wide range they do not work with the same precision as the classical applanation tonometer.

Evaluation Studies as Topic↗
PubMed1989

Charybdotoxin inhibits proliferation and interleukin 2 production in human peripheral blood lymphocytes.

We demonstrate that blockade of the lymphocyte voltage-gated K+ channel by charybdotoxin (CTX) inhibits lymphocyte mitogenesis. Charybdotoxin blocks conductance with a Ki of 0.3 nM and inhibits mitogen- and antigen-stimulated proliferation with a Ki of 0.5 nM. As opposed to the other blockers of the lymphocyte K+ channel, the inhibition of mitogenesis by CTX can be overcome selectively by exogenous recombinant interleukin 2 (IL-2); endogenous levels of IL-2 in the culture supernatants of stimulated cells are decreased by the presence of CTX. Our results suggest that the voltage-gated K+ channel is either directly or indirectly involved in IL-2 synthesis and/or secretion.

4-Aminopyridine↗
PubMed1989

Modulation of K+ currents in human lymphocytes by pH.

1. Using whole-cell patch-clamp techniques, we found that the voltage-dependent K+ conductance in human peripheral blood T lymphocytes is enhanced threefold at alkaline intracellular pH (pHi) compared to acid pHi. This pH dependence can be described by a model having two strongly co-operative proton binding sites with pka 7.15. A similar pHi sensitivity exists for K+ conductance in mitogen-activated cells. 2. The reversal potential, threshold voltage for activation of the K+ conductance, and voltage dependence of steady-state inactivation are not affected by pHi. Activation and inactivation kinetics are also unchanged. 3. Single-channel measurements made in whole-cell patch-clamp mode indicate that the effect of intracellular pH on the amplitudes of single-channel events parallels, but does not wholly account for, the effect of pHi on the macroscopic currents. 4. Lowering extracellular pH (pHo) shifts the threshold for activation of the K+ current to a more depolarized voltage, consistent with a surface charge screening effect. Apparent changes in peak current and activation kinetics at acid pHo can be accounted for by this voltage shift. An additional slowing of inactivation kinetics at low pHo does occur. 5. The relevance of the pH sensitivity of the voltage-gated K+ conductance to lymphocyte mitogenesis and volume regulation is discussed.

Electrophysiology↗
PubMed1989

[Comparative studies of the calibration of new electronic automatic tonometers].

Over the last years the number of newly developed automatic microprocessor controlled tonometers has been increasing. These devices follow totally different measurement principles. Therefore the physical methods for calibration of these tonometers differ widely. Described is the possibility of calibration of new microprocessor-controlled tonometers. First the Tonopen, which follows the Mackay-Marg principle was tested. Its accuracy in measuring the intraocular pressure and its independency of position was examined. Moreover, the non-contact tonometers were tested. Especially the airstream of non-contact tonometers (CT 10, Pulsair) was measured with a Constant Temperature Anemometer (CTA). The topspeed of the airstream was 335 km/h for the CT 10 and 249 km/h for the Pulsair tonometer. The profile of the airstream was paraboloid. The base measured about 5 mm in diameter. For detection of the effect of the airstream to the cornea, a camera was connected over a special interface with the CT 10 and triggered with a flashlight generator. The airstream produced at the moment of pressure measurement an exact applanation of the cornea with a diameter of about 4 mm. The results demonstrate the possibility of physical calibration, but this does not substitute biometrical measurements.

Calibration↗
PubMed1988

Forskolin effects on the voltage-gated K+ conductance of human T cells.

Forskolin, a direct activator of adenylate cyclase, modifies the voltage-dependent K+ conductance of quiescent human peripheral blood T lymphocytes. In the presence of greater than 20 microM forskolin, the average voltage-gated current in whole-cell patch clamp is significantly decreased. The voltage dependence and kinetics of activation are not changed from untreated control cells. However, inactivation becomes biphasic. Much of the current inactivates very quickly (complete in 10 ms), and the remaining outward current inactivates more slowly with a time constant closer to that of control cells. To determine whether this effect is mediated by a rise in intracellular cAMP, cells were preincubated and subsequently voltage-clamped in the presence of other agents that raise the cAMP levels in T cells (isoproterenol plus a phosphodiesterase inhibitor, or dibutyryl cAMP) with no effect on the K+ conductance. Similarly, cells put in whole-cell patch clamp with cAMP, GTP, ATP, and theophylline added to the electrode filling solution showed no change in K+ current. Because other procedures that raise cAMP did not duplicate the effect of forskolin, we investigated the effect of 1,9-dideoxyforskolin, an analogue of forskolin that does not stimulate adenylate cyclase in human lymphocytes. This drug induced changes in the whole-cell K+ conductance identical to those observed with forskolin. Both forskolin and dideoxyforskolin inhibit mitogen-induced proliferation of lymphocytes. Because inhibition of proliferation occurs in the presence of known K+ channel blockers, these results suggest that forskolin has an effect on T cell mitogenesis that is mediated by inhibition of K+ conductance and is independent of cAMP.

Adenylyl Cyclases↗
PubMed1988

19F-nuclear magnetic resonance: measurements of [O2] and pH in biological systems.

19F-nuclear magnetic resonance (NMR) has been used to determine both intracellular pH and oxygen concentrations in cell suspensions. Oxygen concentrations in Paracoccus denitrificans and insulinoma cells, RINm5F, in the NMR probe can be monitored directly by 1/T1 measurements of perfluorotripropylamine (FTPA)/lecithin emulsion added to the suspensions. With FTPA oxygen monitoring, we investigated the relative aeration capabilities of two types of NMR chambers. Both normal and transformed eucaryotic cells can be maintained in either chamber for at least 1-2 h at cytocrits of up to 20-25%, with 30% oxygen saturation and cell viabilities of 90-95%. Similar concentrations of procaryotes were maintained aerobic with high FTPA concentrations in the more efficient of the two NMR chambers. A new precursor molecule for the 19F-NMR pH indicator difluoromethylalanine, the para-chlorophenyl ester, has been tested and used in RINm5F cells and P. denitrificans, neither of which hydrolyzes methyl esters.

Animals↗
PubMed1988

Comparison of ion channels in multidrug-resistant and -sensitive human leukemic cells.

Tumor cell lines selected to grow in the presence of one "natural product" antineoplastic drug often develop cross-resistance to others. This multidrug resistance (MDR) is believed to be a major problem in cancer therapy. Organic Ca2+-channel blockers, such as verapamil, can reverse this resistance and render MDR cells in culture nearly as sensitive to the antineoplastic drugs as the drug-sensitive cells from which they were derived. It has therefore been suggested that Ca2+ channels may play a role in MDR. To determine directly whether there are electrophysiological correlates of MDR, we used whole-cell and single-channel patch-clamp techniques to survey the ion channels in a drug-sensitive human T-cell leukemia line, CCRF-CEM, and a MDR variant, CEM/VLB100. We found no evidence for a voltage-gated Ca2+ channel. However, we did identify three other current/channel types: a voltage-gated tetrodotoxin-sensitive inward current carried by Na+, a voltage-gated labile outward current carried by K+, and a nonselective cation channel reversing at 0 mV. Drug-sensitive and -resistant cells were the same with respect to the level of expression of these channels.

Antineoplastic Agents↗