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Biomedical subjects

R Horn

Publications and source records attributed to R Horn.

At least 19 recordsLinked to original sources
PubMed1992

Chimeric study of sodium channels from rat skeletal and cardiac muscle.

Two isoforms of voltage-dependent Na channels, cloned from rat skeletal muscle, were expressed in Xenopus oocytes. The currents of rSkM1 and rSkM2 differ functionally in 4 properties: (i) tetrodotoxin (TTX) sensitivity, (ii) mu-conotoxin (mu-CTX) sensitivity, (iii) amplitude of single channel currents, and (iv) rate of inactivation. rSkM1 is sensitive to both TTX and mu-CTX. rSkM2 is resistant to both toxins. Currents of rSkM1 have a higher single channel conductance and a slower rate of inactivation than those of rSkM2. We constructed (i) chimeras by interchanging domain 1 (D1) between the two isoforms, (ii) block mutations of 22 amino acids in length that interchanged parts of the loop between transmembrane segments S5 and S6 in both D1 and D4, and (iii) point mutations in the SS2 region of this loop in D1. The TTX sensitivity could be switched between the two isoforms by the exchange of a single amino acid, tyrosine-401 in rSkM1 and cysteine-374 in rSkM2 in SS2 of D1. By contrast most chimeras and point mutants had an intermediate sensitivity to mu-CTX when compared with the wild-type channels. The point mutant rSkM1 (Y401C) had an intermediate single-channel conductance between those of the wild-type isoforms, whereas rSkM2 (C374Y) had a slightly lower conductance than rSkM2. The rate of inactivation was found to be determined by multiple regions of the protein, since chimeras in which D1 was swapped had intermediate rates of inactivation compared with the wild-type isoforms.

Amino Acid Sequence↗
PubMed1992

Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.

The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. The cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the sodium channel multigene family and bears greater than 90% identity to the tetrodotoxin-insensitive sodium channel characteristic of rat heart and of immature and denervated rat skeletal muscle. Northern blot analysis demonstrates an approximately 9.0-kilobase transcript expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. When expressed in Xenopus oocytes, hH1 exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and hH1 is more resistant to block by tetrodotoxin (IC50 = 5.7 microM). hH1 is also resistant to mu-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner.

Amino Acid Sequence↗
PubMed1992

Lidocaine block of human heart sodium channels expressed in Xenopus oocytes.

The tertiary amine lidocaine is used clinically for preventing cardiac arrhythmias, and has been widely studied on mammalian tissue. Xenopus oocytes were used as an expression system to study the effect of lidocaine on a sodium (Na) channel, derived from a full-length human heart (hH1) cDNA clone. The concentration dependence of the lidocaine block of hH1 Na current was consistent with a binding stoichiometry of 1:1. At low frequency stimulation, and at holding potentials < or = 100 mV, the IC50 was 226 microM, comparable to values found in mammalian cardiac cells. Lidocaine also shifted the steady-state inactivation of hH1 Na current to hyperpolarized potentials in a dose-dependent manner. Our experiments suggest that lidocaine block is state dependent, with high affinity for an inactivated state (KI = 11 microM) and low affinity for the resting state (KR = 3.9 mM). The quaternary amine derivative of lidocaine, QX-314, had no effect on Na current at an extracellular concentration of 1 mM.

Animals↗
PubMed1992

Gene expression of differentiation- and dedifferentiation markers in normal and malignant human thyroid tissues.

Steady state mRNA transcript levels of thyroid differentiation markers such as TSH receptor (TSHR), thyroglobulin (Tg) and thyroid peroxidase (TPO) as well as a potential marker of dedifferentiation, c-myc, marker were investigated in patients with thyroid tumors and in normal controls using Northern blot analysis. Blots were normalized by acridine orange staining whereas analysis of beta-actin mRNA levels revealed highly variable levels already in normal tissue suggesting regulation of this "constitutively" expressed gene. Determination of c-myc mRNA revealed increased steady state mRNA levels in anaplastic carcinomas (ATC) as compared to normal tissues. However, in some patients c-myc transcript levels were lower in the tumor than in the adjacent normal tissue reducing the significance of c-myc as a marker of dedifferentiation. High levels of TSH mRNA were found in control thyroids, whereas in ATC no normal TSHR mRNA was detected. In PTC and follicular thyroid carcinomas (FTC) the transcripts varied from increased to markedly reduced levels. In one patient with FTC 2 independent preparations of the tumor revealed different results, undetectable and clearly detectable TSHR mRNA levels. Xenotransplantation of this tissue on nude rats showed a variable expression pattern in the individual xenotransplantations suggesting heterogeneity of the tumor tissue. Tg and TPO mRNA were strongly expressed in normal tissues and completely lost in all ATC. In differentiated thyroid tumors the transcript levels of Tg and TPO varied from normal to complete loss of expression of either Tg or TPO, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridine Orange↗
PubMed1992

Susceptibilities of members of the Bacteroides fragilis group to 11 antimicrobial agents.

The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to 11 antimicrobial agents were determined by the broth microdilution method of the National Committee for Clinical Laboratory Standards. All isolates were susceptible to imipenem and ticarcillin-clavulanic acid. The rates of resistance to cefoxitin and clindamycin were low (4 and 6%, respectively), while those to ceftizoxime and cefotetan were higher (10.5 and 24%, respectively).

Anti-Bacterial Agents↗
PubMed1992

[Recurrent inguinal hernias: surgery with transversalis fascia repair].

Some authors recommend different prosthetic repairs for treatment of recurrent groin hernia. In our institution groin hernias are treated by a modified Shouldice-repair, which considers the transversalis fascia layer only. In this prospective study 240 consecutive patients with 298 groin hernias were operated on. 46 patients were treated for 53 recurrent hernias. It was possible to carry out the operative procedure of transversalis plasty in all recurrent cases. 90% of these patients were followed-up by personal examination after a median of 26 months after operation (range 12-36 months). 89% of the patients with primary operation have been checked 15 months postoperatively. 2 patients (4.5%) of the recurrent hernias had a recurrence. This compares well with the 3.2% recurrence rate (7 patients) in the patients with primary hernias. The difference is not significant (p greater than 0.5). The only observed difference between recurrent and primary hernias was in the rate of testicular atrophy (6.8% for recurrent and 0% for primary hernias). According to our experience large prosthetic repairs are not necessary for the common case of recurrent groin hernia, but may be useful in specially selected situations.

Adult↗
PubMed1992

[Anterior knee laxity in a healthy patient sample].

A prospective study investigates anterior knee laxity in 100 healthy subjects (mean age 24.5 years). Testing was performed by two examiners either clinically by Lachman test or by means of KT-1000 arthrometer. Mean anterior tibial translation was 4 mm for the right and 4.3 mm for the left knee when tested clinically. With use of KT-1000 at 89 Newton results were 4.6 mm and 4.0 mm, respectively. Clinical measurements revealed an inter-examiner difference of 0 to 1 mm in 77% of right and 80% of left knees. In the remainder difference was more than 1 mm. On apparative testing the two examiners obtained similar results at 67 Newton. Measurements differed increasingly, however, at 89 Newton and 134 Newton. In conclusion, the use of KT-1000 arthrometer in routine assessment of anterior knee laxity offers no advantage over clinical testing alone.

Adult↗
PubMed1991

[Cold-induced pathology at high altitude].

Cold injury is an objective danger in mountain climbing as well as in many outdoor and recreational sports such as skiing, fishing, etc. Symptoms are easily recognizable by the experienced, and prevention is mostly possible. Cold injury should be divided by pathological means in general hypothermia and local frostbite injuries. Life-threatening deep hypothermia with coma and insufficient circulation or cardiac arrest is reversible under the condition of sufficient core rewarming, for instance by CEC. Because of the big tolerance of hypothermic patients to hypoxia, clinical death is not like biological death and therefore reversible. Local frostbite is not life-threatening, but has often deleterious effects. Rapid rewarming in warm water of 37 to 42 degrees C is mandatory. After rewarming, the difference between superficial and deep frostbite can be established. Scintigraphy seems to be of great help in setting early prognosis. Daily sterile treatment of the injury, whirlpool bath and prevention of infections belong to standard treatment. There are little objective informations about the role of vasodilators, anticoagulants, antibiotics, sympathectomy and others. Early experience with Prostavasine seems to bee encouraging.

Adult↗
PubMed1991

Failure to elicit neuronal macroscopic mechanosensitive currents anticipated by single-channel studies.

Mechanosensitive channels can be observed in most cell types during single-channel recording and have been implicated in many cellular processes. Potassium-selective single-channel currents, both stretch-activated and stretch-inactivated, can be observed in growth cones and cell bodies of Lymnaea stagnalis neurons. Equivalent macroscopic mechanosensitive currents could not, however, be elicited while applying various mechanical stimuli. This discrepancy suggests that single-channel mechanosensitivity is an artifact of patch recording.

Animals↗
PubMed1991

A mitochondrial 16 kDa protein is associated with cytoplasmic male sterility in sunflower.

Cytoplasmic male-sterile lines CMS89 and CMSBaso of sunflower (Helianthus annuus) differ from the fertile lines HA89 and Baso in a mitochondrial DNA sequence in the vicinity of the atpA gene. In addition, the transcriptional pattern of the atpA gene is changed in male-sterile lines compared to fertile ones. Besides one main transcript in the fertile lines, the male-sterile lines additionally show larger transcripts. Investigation of Baso and CMSBaso revealed that the two fertility-restored lines of CMS89 have the same transcripts as CMSBaso or a combination of CMSBaso and CMS89. Comparing the mitochondrial in organello translation products we observed a unique 16 kDa protein, which is expressed in male-sterile lines carrying the H. petiolaris cytoplasm but is not detectable in fertile lines with H. annuus cytoplasm. The 16 kDa protein can also be observed in restored lines but not in H. petiolaris. As the expression of the 16 kDa polypeptide seems to be linked to the interspecific cross between H. petiolaris and H. annuus it may play a role in CMS. By different criteria such as molecular mass, isoelectric point and peptide fingerprinting the alpha subunit of the F1-ATPase of male-sterile and fertile lines is very similar if not identical.

Crosses, Genetic↗
PubMed1991

Cytoplasmic male sterility in sunflower is correlated with the co-transcription of a new open reading frame with the atpA gene.

The organization and expression of the mitochondrial (mt) genome of fertile, male-sterile and restored lines of Helianthus annuus and of H. petiolaris were compared to identify alterations which might lead to cytoplasmic male sterility (CMS). The mtDNAs of fertile and male-sterile lines differ by an 11 kb inversion and a 5 kb insertion. The rearrangements seem to be the result of recombination events within an inverted repeat of 261 bp. Detectable alterations in the transcript pattern of the rearranged mtDNA regions are restricted to the atpA locus. The male-sterile line CMSBaso shows three additional transcripts of the atpA locus of about 2500, 1200 and 250 nucleotides which are not detectable in Baso. However, the coding sequences of the atpA gene are entirely identical in the fertile line Baso and the male-sterile line CMSBaso. But a new open reading frame (orfH522) of 522 nucleotides is co-transcribed with the atpA gene as an additional larger transcript of about 2500 nucleotides in CMSBaso. orfH522 is also included in a second additional transcript of about 1200 nucleotides. The predicted translation product of orfH522 might play a role in CMS in sunflower.

Amino Acid Sequence↗
PubMed1991

Diffusion of nystatin in plasma membrane is inhibited by a glass-membrane seal.

In perforated patch recording, the pore former nystatin is incorporated into a cell-attached patch, to increase its conductance. The possibility of lateral diffusion of nystatin through the membrane and under the glass-membrane seal was examined by reversing the nystatin gradient. Namely, a cell-attached patch on a cell was examined while placing nystatin into the bath. The reversal potential and current-voltage relationship of single Ca2+ activated K+ channels in the patch were readily changed by varying the K+ concentration in the bath, showing that nystatin was active in the cell membrane outside of the patch. However, the patch itself did not become leaky. The absence of a conductance induced in the patch by the nystatin in the rest of the plasma membrane of the cell suggests that the lateral diffusion of nystatin is inhibited by the glass-membrane seal.

Biophysical Phenomena↗
PubMed1991

A [Na+]o-independent, pHo-dependent mechanism for reduction of intracellular [Ca2+] after influx through Ca2+ channels in mouse pituitary cells.

The effect of extracellular pH (pHo) on the duration of calcium-dependent chloride currents (ICl(Ca] was studied in voltage clamped AtT-20 pituitary cells. ICl(Ca) was activated by Ca2+ influx through plasma membrane Ca2+ channels, which were opened by step depolarization to voltages between -20 and +60 mV. Increasing pHo from 7.3 to 8.0 reversibly prolonged ICl(Ca) tail currents in perforated patch recordings from cells bathed in both Na(+)-containing and Na(+)-free solutions. This prolongation was prevented in standard whole cell recordings when the pipette solution contained 0.5 mM EGTA. The effects of raised pHo were not due to alteration of intracellular pH, since tail current prolongation still occurred when intracellular pH was buffered at 7.3 with 80 mM HEPES. The prolongation of ICl(Ca) at pHo 8 could not be accounted for by a direct action on Ca2+ channels, since tail currents were prolonged when pHo was changed rapidly during the tail current, after all Ca2+ channels were closed. The effects of increasing pHo on ICl(Ca) also could not be explained by a direct action on Cl- channels, since changing to pHo 8 did not prolong Cl- tail currents when intracellular Ca2+ concentration [( Ca2+]i) was fixed by EGTA in whole cell recordings. Raising pHo did, however, prolong depolarization-evoked [Ca2+]i transients, measured directly with the Ca2+ indicator dye, fura-2. Taken together, these data demonstrate the presence of a Na(+)-independent, pHo-sensitive mechanism for reduction of [Ca2+]i after influx through Ca2+ channels. This mechanism is associated with the plasma membrane, and is active on a time scale that is relevant to the duration of single action potentials in these cells. We suggest that this mechanism is the plasma membrane Ca2+ ATPase.

Action Potentials↗
PubMed1991

Control of action potentials and Ca2+ influx by the Ca(2+)-dependent chloride current in mouse pituitary cells.

1. Perforated patch recording was used to examine the influence of the calcium-dependent chloride current (iCl(Ca)) on Ca2+ action potentials in AtT-20 pituitary cells. The calculated chloride equilibrium potential (ECl) was adjusted by changing either intracellular or extracellular [Cl-]. Action potential duration varied as a function of ECl. When ECl was set at -21 mV, both spontaneous and evoked action potentials displayed a long plateau phase between -20 and -25 mV, which typically lasted for several seconds. Setting ECl to more negative potentials resulted in briefer action potentials; at an ECl of -52 mV, no plateau phase was evident. Spontaneous depolarization and action potential firing still occurred when ECl was negative to firing threshold, which indicates that the slow depolarizing wave that precedes the firing of spontaneous action potentials does not require activation of ICl(Ca). 2. In voltage clamp experiments the magnitude of ICl(Ca) diminished slowly during a prolonged depolarization, over a time course that coincided with action potential termination. 3. Niflumic acid (100 microM) blocked ICl(Ca) by 90% but had no effect on either K+ or Ca2+ currents. This concentration of niflumic acid eliminated the plateau phase, but did not prevent the firing, of Ca2+ action potentials. 4. Internal [Ca2+] was measured photometrically after loading cells with the Ca2+ indicator dye, Fura-2. Under voltage clamp conditions, concentrations of niflumic acid (30-100 microM) that blocked depolarization-evoked ICl(Ca) had little or no effect on simultaneously recorded Ca2+ transients. Perforated patch recording from Fura-loaded cells showed that action potentials were temporally associated with transient increases in intracellular [Ca2+]. Niflumic acid (30-100 microM) disrupted the rhythmic firing of spontaneous action potentials and associated intracellular Ca2+ transients. 5. Fluorescent measurements of Ca2+ transients were also made in cells unperturbed by patch recording, and were used as a measure of action potential duration in the absence of experimental alteration of internal [Cl-]. Spontaneous Ca2+ transients were of long duration (approximately 2 s), which suggests that intracellular [Cl-] is relatively high (40-50 mM) in these cells. The spontaneous Ca2+ transients were inhibited by niflumic acid. 6. Niflumic acid up to 100 microM, had neglible effects on either basal or stimulated (by 2 microM-(+/-)-isoprenaline) hormone secretion, as shown by radioimmunoassay of adrenocortotrophic hormone release.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

[Computer-assisted determination of the pharmacokinetic parameters of Solupront after intrauterine administration in cattle].

The drug "Solupront" a sulfonamide was clinical tested in healthy heifers and cows with endometritis, retentio secundinarum etc. The test-results were evaluated with the computer-program "Phakimo". The pharmacokinetic parameters show that there are similar relationships between the extravasal and the intravasal application of this osmochemotherapeutic. A retard of absorption is shown in dioestrus and in prooestrus. If there are pathological signs in uterus, the rate of absorption of the drug is higher and the excretion via urine is more quickly, too. The effect of the sulfonamide in the drug "Solupront" is impaired after application in the uterus in order of the quick absorption, of distribution and excretion and also in order of dilution by lochia and by interaction with p-aminobenzoic acid.

Administration, Intravaginal↗