Modulation of the beta-adrenergic response in cultured rat heart cells

Incubation of rocker-cultured neonatal rat heart cells with 3 mM L(+)-lactate led to a sharp increase in the sensitivity of cardiomyocytes to the beta-adrenergic agonist isoprenaline, as measured by their chronotropic response. This effect was accompanied by a reduction in the arachidonic acid content of the total phospholipids. The phospholipase A₂-activator melittin as well as free arachidonic acid induced this supersensitivity to the same degree. On the other hand, the L(+)-lactate-evoked supersensitivity could be blocked by the phospholipase A₂ inhibitors mepacrine and n-bromophenacyl-bromide, suggesting an involvement of phospholipase A₂ in the process of beta-adrenergic sensitization. The sensitizing action of arachidonic acid was blocked by the lipoxygenase inhibitors esculetin and nordihydroguaiaretic acid, but not by the cyclooxygenase inhibitor indomethacin. Supersensitivity was likewise evoked by 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), but not by 5-S-HPETE or 5-S-HETE. These findings suggest that the phospholipase A₂-15-lipoxygenase pathway plays a role in the induction of beta-adrenergic supersensitivity in the cultured cardiomyocytes and point to a new physiological role of the lipoxygenase product 15-S-HETE.Abbreviations NDGA nordihydroguaiaretic acid - HETE hydroeicosatetraenoic acid - HPETE hydroperoxyeicosatetraenoic acid     

Taurine Levels in Discrete Brain Nuclei of Rats

Concentrations of taurine have been measured in 44 microdissected rat brain nuclei or areas. Taurine is ubiquitously present and distributed unevenly in the rat brain: the ratio of the highest (pyriform cortex) to lowest (midbrain reticular formation) concentrations is 4.7:1. High taurine levels were found in cerebral cortical areas, caudate-putamen, cerebellum, median eminence, and supraoptic nucleus. Acute pain stress reduced taurine levels in the hypothalamus and the lower brainstem nuclei but not in cortical areas. Increased locomotor and behavioral activities following a high dose of amphetamine elevated taurine concentrations significantly in the substantia nigra and locus ceruleus.     

Contractile properties of intercostal muscles and their functional significance

To have some insight into the functional coupling between the parasternal intercostals (PS) and the diaphragm (DPM), we have examined the isometric contractile properties of bundles from canine PS and DPM muscles. Bundles of external (EXT) and internal (INT) interosseous intercostals were studied for comparison. In addition we have related sonometrically measured length of the intercostals in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We found that 1) intercostal twitch speed is significantly faster than DPM, thus displacing their relative force-frequency curve to the right of that of the DPM; 2) the ascending limb of the active length-tension curve of all intercostals lies below the DPM curve; i.e., at 85% Lo, PS force is 46% of maximal force (Po), whereas DPM force is still 87% Po; 3) for any given length change beyond Lo, all intercostals generate greater passive tension than the DPM; 4) Po is greater for the intercostals than the DPM; and 5) at supine FRC, both EXT and INT in dogs are nearly operating at Lo, whereas the PS are operating at a length greater than Lo. We conclude that 1) PS produce less force than DPM during breathing efforts involving low- (10-20 Hz) stimulation frequencies, but they generate more force than DPM when high- (greater than 50 Hz) stimulation frequencies are required; and 2) the pressure-generating ability of the PS is better preserved than that of the DPM with increases in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thioredoxins and the redox modulation of glucose-6-phosphate dehydrogenase in Anabaena sp. strain PCC 7120 vegetative cells and heterocysts.

Glucose-6-phosphate dehydrogenase (G6PDH) was isolated from heterocysts and vegetative cells of Anabaena sp. strain PCC 7120. Both enzyme preparations proved to be more active in their oxidized than in their reduced forms. At least one protein with thioredoxin activity was found in Anabaena sp. which, if reduced with dithiothreitol, deactivated the G6PDH preparations. The deactivated heterocyst G6PDH could be reactivated neither by O2 nor by oxidized thioredoxin. Reactivation of the enzyme was, however, achieved by oxidized glutathione or H2O2. The active form of Anabaena G6PDH was readily deactivated by heterologous thioredoxin(s). The Anabaena thioredoxin(s) modulated heterologous enzymes.     

Lysis of autologous tumor cells by blood lymphocytes tested at the time of surgery

Summary Lymphocyte-mediated lysis of autologous tumor cells (autologous lymphocyte cytotoxocity ALC) was tested at the time of surgery in 108 patients (46 squamous cell carcinomas of the lung, 25 adenocarcinomas of the lung, 19 soft tissue sarcomas and 18 osteosarcomas). The clinical course of these patients in relation to the test results has been published previously. The group was evaluated again after an extended observation time, now with a mean of 80.2 months (range 36–108). The test was rarely positive in patients with metastasis (2 out of 28 experiments).There was a correlation between the ALC results and the postsurgical clinical course for patients without detectable metastasis in that (1) a negative test was invariably a bad prognostic sign, i.e., all 32 patients with negative ALC died within 3 years (mean survival time 16.1 months). (2) The remission and survival times were longer for the ALC positive patients (p<0.001). (3) All 37 individuals who are alive at present without recurrence belong to the reactive group.The ALC results correlated with the clinical course in 88% of patients. The correlation was highest for the groups of soft tissue sarcoma and adenocarcinoma of the lung. There was no correlation between killing of K562 cells and ALC, or between lymphoproliferative response to PHA and ALC reactivity.     

On the ancestral form of true organ of fructification in the saprophytic stage of the dermatophytes of the faviform group: Favomicrosporon pinettii,N.SP. and its perfect form: Anixiopsis stercoraria (hansen) hansen, 1897

Summary The discovery of the hidden, built-in macroconidia in the four members of the Faviform Group of the dermatophytes, i.e.,Achorion schoenleinii, Trichophyton violaceum, Trichophyton verrucosum andMicrosporon ferrugineum, is described.To bring the hidden, built-in macroconidia to full fructification, i.e., to force the production of imperfect and perfect organs of fructification (macroconidia, cleistothecia), two entirely different techniques have been used: 1) the hair-soil method, 2) the yeast extract method.The two techniques, entirely independent from each other, yielded the same result: the ancestral form of the four members of the Faviform Group of dermatophytes. The imperfect form is described asFavomicrosporon pinettii,Benedek, 1965, sp. nov. The perfect form isAnixiopsis stercoraria (Hansen)Hansen, 1897.The ancestral form was found not only in and cultured from the strains of those dermatophytes derived from pathological material, but it was also recovered from its saprophytic habitat, from the soil (potting soil).

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Zusammenfassung Die Entdeckung der verborgenen, eingebauten Makrokonidien in den vier Representanten der Faviformen Gruppe der Dermatophyten, i.e.Achorion schoenleinii, T. violaceum, T. verrucosum, Microsporon ferrugineum, wird beschrieben.Um die verborgenen, eingebauten Makrokonidien zur vollen Fruchtbildung zu bringen, i.e. um die Produktion der imperfekten und perfekten Organe der Fruktifikation (Makrokonidien, Kleistothecien) zu erzwingen, sind zwei völlig verschiedene Methoden benutzt worden: 1) die Haar-Erde-Methode, und 2) die Hefeextrakt-Methode.Beide Methoden, völlig unabhängig von einander, haben zu demselben Ergebnis geführt, i.e. zur Entdeckung der Urform von den vier Representanten der Faviformen Gruppe der Dermatophyten. Die imperfekte Form wird alsFavomicrosporon pinettii,Benedek, 1965, sp. nov. beschrieben. Die perfekte Form istAnixiopsis stercoraria (Hansen)Hansen, 1897.Die ancestrale Form wurde nicht nur aus den Stämmen jener Dermatophyten gezüchtet, die aus pathologischen Produkten gewonnen worden sind, sondern auch aus dem natürlichen Habitat: von der Erde (potting soil).

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Résumé La découverte des macroconidies occultes et encastrées dans les quatre membres du Groupe Faviforme des dermatophytes:Achorion schoenleinii, Trichophyton violaceum, Trichophyton verrucosum etMicrosporon ferrugineum, est décrite.Pour forcer les macroconidies occultes et encastrées à la fructification complète, i.e. de produire des organs de reproduction imparfaits et parfaits, macroconidies et cleistothecia, on a fait l'usage de deux techniques complètement différentes: 1) des cheveux sur sol et 2) de l'extraction de levure.Toutes les deux méthodes, complètement indépendantes l'une de l'autre, ont produit le même résultat: la forme ancestrale des quatre membres de la Groupe Faviforme des dermatophytes. La forme imparfaite est décrite commeFavomicrosporon pinettii,Benedek, 1965, sp. nov. et la forme parfaite commeAnixiopsis stercoraria (Hansen)Hansen, 1897.La forme ancestrale a été trouvée non seulement dans les souches des dermatophytes indiquées et en cultivées, provenantes des produits pathologiques, mais aussi du sol, du terrain jardinier.

     

Modulation of Rat Brain Cortical α-Adrenoceptors by Treatment with Hydrocortisone for 10 Days

The role of glucocorticoids in the modulation of central alpha 2-receptor mechanisms was investigated by in vitro receptor binding studies. [3H]Clonidine and [3H]idazoxan were used as radioligands. The alpha 2-receptor subtypes and guanine nucleotide sensitivity were studied in homologue and heterologue displacement experiments following hydrocortisone treatment (25 mg/kg s.c.) for 10 days. High and low agonist affinity states of the alpha 2-receptor could be identified in 3H-antagonist-agonist and 3H-agonist-antagonist displacement experiments, which may correspond to different regulatory protein-nucleotide associated forms of the receptor. In the presence of 10 microM GTP, the high-affinity binding was depressed. Following hydrocortisone treatment, there was no detectable change either in the affinity or the binding site concentration of clonidine in homologue displacement ("cold saturation") experiments. The affinity of idazoxan, however, was depressed. The effect of GTP was similar to the controls in this experimental arrangement. In contrast, in heterologue binding studies the high-affinity binding site was not demonstrable and the amount of low-affinity binding increased following the hydrocortisone treatment. The high-affinity site reappeared in the presence of GTP. The change in GTP sensitivity suggests that the nucleotide regulatory system may be involved in the action of adrenal steroids on central alpha 2-receptoral mechanisms.     

Queuine is incorporated into brain transfer RNA

Pig brain tRNA was assayed for the presence of queuosine in the first position of the anticodon for each of the Q-family of tRNAs (aspartyl, asparaginyl, histidyl and tyrosyl). The brain tRNA was aminoacylated with each of the four amino acids and the aminoacylated tRNA's analyzed by RPC-5 chromatography. The results of this study show that for all four tRNAs of the family, queuine is substituted for guanine in virtually 100% of the anticodons. Therefore, it can be concluded that queuine is able to cross the blood-brain barrier and that brain contains quanine-queuine tRNA transglycosylase, the enzyme responsible for the excision of guanine from the orginal transcipts of these tRNAs and insertion of queuine. The determination of whether the tRNA contained queuine was made from the elution profile of the RPC-5 chromatrograms and the results confirmed by a change in the RPC-5 elution profile when the tRNAs were reacted with BrCN or NaIO₄.