1. Intravenous injections of lobeline HCl into twenty‐six normal young male human volunteers produced sensations of choking, pressure or fumes in the throat and upper chest at a mean threshold dose of 12 micrograms kg‐1. 2. Reflex changes in breathing pattern usually appeared just before the sensations. Increasing the dose of lobeline increased the intensity of the sensations gradually until a dry cough appeared at a mean threshold dose of 24.3 micrograms kg‐1. At these doses there was a mean difference of 0.3s in the latencies for sensation and respiratory reflex; in four subjects there was no difference at all. 3. In cats anaesthetized with 35 mg kg‐1 sodium pentobarbitone, injecting 25‐67 micrograms kg‐1 lobeline into the right atrium sensitized thirteen out of seventeen rapidly adapting receptors (RARs). In three out of four cats lobeline had no excitatory effect on the RARs in the absence of normal activity (i.e. when it was injected while artificial respiration was suspended), but on restarting the respiration the activity increased greatly. After injecting lobeline, the activity increased during inflation or deflation or in both phases of the respiratory cycle. It also increased greatly during deflation produced by suction of air from the lungs after lobeline. Such presumed increased activity in the RARs of man produced by forced expiration to residual volume at the time lobeline‐induced sensations were expected did not enhance the sensations in any subject. 4. In all the subjects tested, forced expiration alone, which should stimulate RARs, never produced a dry cough or sensations similar to those produced by lobeline.(ABSTRACT TRUNCATED AT 250 WORDS)
SUMMARY1. Experiments carried out on anaesthetized cats showed that increasing blood flow, through the lobes of a lung, by 133 % (S.E. 33 %) generated an average of 0 75 impulses/sec (S.E. 0.3) in ten almost silent J receptors. Equivalent activity was produced by injecting 12-18 /tg phenyl diguanide/kg into the right atrium. Such activity caused marked reflex effects, i.e. apnoea, rapid shallow breathing and reduction in the knee jerk.2. The reflex effects of J receptors were studied after blocking the activity from cardiac receptors by intrapericardial injections of xylocaine. This was necessary because left atrial injections of phenyl diguanide produced reflex respiratory effects and inhibition of the knee jerk.3. Hypoxia, but not hypercapnia, attenuated the reflex effects of J receptors, apnoea being abolished if the Pa,02 fell below 35 mmHg. This was a central effect as it occurred in spite of increased activity of J receptors following phenyl diguanide, and effects of hypoxia persisted after cutting both carotid nerves.4. The only invariable reflex effect of J receptors was a reduction in the total number and the average frequency of phrenic impulses in each breath. The changes in inspiratory time (ti) and expiratory time (te) following apnoea were variable although most frequently both were reduced. In about half the observations the first effect before the apnoea was a reduction in ti, in the other half it was a reduction in te. It was, concluded that an input from J receptors inhibits inspiratory and expiratory mechanisms directly.5. In some cats apnoea and rapid shallow breathing produced by J receptors continued after interrupting their activity by vagotomy and this did not diminish the reduction in ti or te; in other cats it did. The reduction in te was at times quite independent of changes in ti, i.e. pulmonary stretch receptor activity.6. It was concluded that J receptors must be stimulated during moderate exercise to levels that produce marked respiratory reflex effects and inhibition of muscles.
Xylanase encoding gene (1,224 bp) from Geobacillus thermodenitrificans was cloned in pET28a (+) vector and successfully expressed in Escherichia coli BL21 (DE3). The deduced amino acid sequence analysis revealed homology with that of glycosyl hydrolase (GH) 10 family with a high molecular mass (50 kDa). The purified recombinant xylanase is optimally active at pH 9.0 and 70 °C with T(1/2) of 10 min at 80 °C, and retains greater than 85 % activity after exposure to 70 °C for 180 min. The enzyme liberates xylose as well as xylooligosaccharides from birchwood xylan and agro-residues, and therefore, this is an endoxylanase. The xylan hydrolytic products (xylooligosaccharides, xylose, and xylobiose) find application as prebiotics and in the production of bioethanol. The xylanase being thermostable and alkalistable, it has released chromophores and phenolics from the residual lignin of pulps, suggesting its utility in mitigating chlorine requirement in pulp bleaching.
An extremely thermophilic bacterial isolate that produces a high titer of thermostable endoxylanase and β-xylosidase extracellularly in an inducible manner was identified as Geobacillus thermodenitrificans TSAA1. The distinctive features of this strain are alkalitolerance and halotolerance. The endoxylanase is active over a broad range of pH (5.0-10.0) and temperatures (30-100 °C) with optima at pH 7.5 and 70 °C, while β-xylosidase is optimally active at pH 7.0 and 60 °C. The T 1/2 values of the endoxylanase and β-xylosidase are 30 min at 80 °C, and 180 min at 70 °C, respectively. The endoxylanase activity is stimulated by dithiothreitol, but inhibited strongly by EDAC and Woodward's reagent K. N-BS and DEPC strongly inhibited β-xylosidase. MALDI-ToF (MS/MS) analysis of tryptic digest of β-xylosidase revealed similarity with that of G. thermodenitrificans NG 80-2, and suggested that this belongs to the GH 52 glycosyl hydrolase super family. The action of endoxylanase on birch wood xylan and agro-residues such as wheat bran and wheat straw liberated xylooligosaccharides similar to endoxylanases of the family 10 glycoside hydrolases, while the enzyme preparation having both endoxylanase and β-xylosidase liberated xylose as main hydrolysis product.
The sensations evoked by the injection of lobeline into the right antecubital vein were studied in 8 subjects after bilateral lung transplantation and 10 control subjects. In control subjects, two distinct sensations were experienced. There was an early noxious sensation (onset ≈10 s) followed by a late sensation of breathlessness (onset ≈26 s) associated with involuntary hyperventilation. The early sensation was accompanied by respiratory and cardiovascular changes. In contrast to control subjects, the early respiratory events and the noxious sensations evoked by injections of lobeline (18‐60 μg kg−1) did not occur in subjects with recent bilateral lung transplantation. This suggests that the early respiratory sensations are mediated by the discharge of receptors in the lungs. The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline. In control subjects, but not transplant subjects, there was a consistent decrease in mean arterial pressure associated with the lobeline injection. This suggests that pulmonary afferents mediate the hypotension. For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned. This suggests that some functional reinnervation of pulmonary afferents may occur.
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