Prolonged poststimulation inhibition of bladder activity induced by tibial nerve stimulation in cats

Inhibition of bladder activity by tibial nerve stimulation was investigated in α-chloralose-anesthetized cats with an intact spinal cord. Short-duration (3-5 min) tibial nerve stimulation at both low (5 Hz) and high (30 Hz) frequencies applied repeatedly during rhythmic isovolumetric bladder contractions was effective in inhibiting reflex bladder activity. Both frequencies of stimulation were also effective in inducing inhibition that persisted after the termination of the stimulation. The poststimulation inhibitory effect induced by the short-duration stimulation significantly increased bladder capacity to 181.6 ± 24.36% of the control capacity measured before applying the stimulation. Thirty-minute continuous stimulation induced prolonged poststimulation inhibition of bladder activity, which lasted for more than 2 h and significantly increased bladder capacity to 161.1 ± 2.9% of the control capacity. During the poststimulation periods, 5-Hz stimulation applied during the cystometrogram elicited a further increase (~30% on average) in bladder capacity, but 30-Hz stimulation was ineffective. These results in cats support the clinical observation that tibial nerve neuromodulation induces a long-lasting poststimulation inhibitory effect that is useful in treating overactive bladder symptoms.     

Changes in the activity of plasma beta-endorphin-like-immunoreactivity induced by transcutaneous stimulation of the brain

A newly devised technique of electrical transcutaneous brain stimulation has been applied to a population of cephalalgic patients in order to assess its proficiency in pain relieving and in increasing the concentration of serum endorphins. A significant pain relief associated with an increase in serum endorphins has been obtained only in those patients in which clinical and instrumental evaluations had identified the headache as one of "organic" origin. By contrast both in "non organic" and in control subjects the technique has proved to be effectiveless. Our results suggest that transcutaneous electrical brain stimulation can affect the release of endogenous opioids relieving pain at least in selected patients.     

The fine structural localization of acid phosphatase in the prolactin cell of the teleost pituitary following the stimulation and inhibition of secretory activity

Fine structural studies have been made upon the prolactin cells of Poecilia latipinna when the fish is subjected to a series of changes in its environmental salinity. Under the regimen employed it is shown that the secretory mechanism of the cell is initially stimulated in fresh water and then inhibited in salt water. The latter event is accompanied by the appearance of demonstrable acid phosphatase activity within the Golgi complex and by the formation of a variety of acid phosphatase-positive bodies. The way in which this acid hydrolase activity is concerned with the removal of surplus secretory granules is described and discussed.     

Calcium lonophore-induced stimulation of secretory activity in Chlamydomonas reinhardii

The cell-wall lysin in gametes from Chlamydomonas reinhardii which under normal mating conditions is activated by flagellar cell contact was found to be susceptible to stimulation by the antibiotic ionophore A 23187 provided that CA²⁺ was included in the medium. Ionophore-induced release of the cell-wall lysin did not deend on the mating type or the gametic state of the cells. Vegetative cells which normally do not exhibit any mating capacity reacted with cell-wall lysis like gametes stimulated by cell contact.Ionophore-dependent Ca²⁺-transfer across the cell membranes generated a signal for cell-wall lysis only in cells with intact flagella. Deflagellated cells did not respond to A 23187 before regeneration of the amputated organelles. Another indication for a possible role of flagella in Ca²⁺-mediated cell-wall lysis was obtained from a conditional flagellar-assembly mutant of C. reinhardii which had been isolated and described by Huang et al. (1977). Upon shift-up the mutant strain immediately became unresponsive to A 23187 and Ca²⁺ but regained susceptibility soon after being retransferred to permissive conditions (20°C).     

Changes in cell density induced by Isopaque

Incubation in culture medium at 37 °C of normal mononuclear leukocytes, isolated on Ficoll-Isopaque, resulted in a general decrease in the specific gravity of these cells. Monocytes and lymphocytes could then be recognized as separate populations in the density distribution profile. This decrease of the cell density was inhibited by lowering the temperature to 0 °C or by the addition of Ficoll-Isopaque to the incubation medium. After pre-incubation at 37 °C, renewed contact between mononuclear leukocytes and Ficoll-Isopaque induced a general increase of the cell density. Monocytes and thymidine-incorporating lymphocytes were affected to a greater extent than small lymphocytes. The increase of the specific gravity of monocytes was time and temperature dependent. The density shift of the thymidine-incorporating lymphocytes was only time dependent. The change in the density of small lymphocytes was dependent on the combination of contact with Ficoll-Isopaque and centrifugal stress. Isopaque was the agent responsible for the effects. It is concluded that the use of small molecular substances such as Isopaque as a constituent of density gradients may introduce reversible changes of the specific gravity of mononuclear leukocytes which may limit the separation of mononuclear sub-populations.     

Thymus cell traffic induced by antigen stimulation

Spleens of adult mice immunized with either RSA or RGG responded in vitro to DNP-RSA or DNP-RGG, respectively, at a significantly higher rate than spleens of untreated mice. Stimulation in vitro could be achieved by short pulses of the antigen (5–15 min). It was found that thymectomy prior to injection of the carrier protein interfered with the subsequent response in vitro to the hapten-carrier conjugate, and that this was much more pronounced in 8- to 10-day-old mice than in older mice. It is suggested that antigen stimulation in vivo triggers thymus cell migration. Although this is by no means the only mechanism accountable for manifestation of the carrier effect, it may represent a device for amplification of the immune response in vivo.     

The activity and malate inhibition/stimulation of phosphoenolpyruvate-carboxylase in crassulacean-acid-metabolism plants in their natural environment

The effect of environmental conditions, temperature, relative humidity, and light, together with the regulation of PEPC (phosphoenolpyruvate-carboxylase) activity by malate and pH on CAM (crassulacean acid metabolism), was studied in members of the Mesembryanthemaceae in their natural environment, the southern Namib desert. It was found that during a 24 h period the characteristics of PEPC change. Before sunrise the activity is higher when measured at pH 7 than 8. With bright sunlight the activity measured at pH 7 drops to 20% of its pre-sunrise value, the activity only recovers gradually after malate disappearance and stays constant throughout the night. When measured at pH 8, PEPC shows an opposite behavior, i.e., activity increases in bright sunlight and declines as the pH 7 activity increases. A day-night oscillation in the capacity of malate to stimulate or inhibit PEPC was found. During the day malate inhibits about 90% of the PEPC activity at both pH 7 and 8. After sunset there is a sudden decrease in this inhibition and, at pH 8, malate stimulates the activity by 50%. At pH 7 the stimulation was less.Both stomatal conductance and malate formation were found to increase only when the relative humidity at night rose to 80%. Changes in the properties of the PEPC coincided with the exposure to bright sunlight and changes in leaf temperature. The importance of these metabolic and environmental controls on the regulation of CAM in the Mesembryanthemaceae will be discussed.Abbreviations CAM crassulacean acid metabolism - PEP phosphoenolpyruvate - PEPC PEP-carboxylase     

Synthesis of chiral phosphoantigens and their activity in gamma delta T cell stimulation

Gammadelta T cells expressing Vgamma2Vdelta2 T cell receptors are activated by a broad range of phosphorus-containing small molecules, termed phosphoantigens, and are of interest in the context of the chemotherapy of B cell malignancies. Here, we report the synthesis of four pairs of chiral phosphoantigens: the bromohydrins of isopentenyl diphosphate (Phosphostim), the epoxides of isopentenyl diphosphate (EIPP); and the corresponding bromohydrin and epoxide analogs of but-3-enyl diphosphate. The ability of each compound to stimulate human Vgamma2Vdelta2 T cells was determined by TNF-alpha release and cell proliferation. In these assays, the (R)-bromohydrin diphosphates were, on average, about twice as active as the (S)-bromohydrin diphosphates. In contrast, the (S)-form of EIPP was about twice as active as (R)-EIPP. The activities of the epoxy but-3-enyl diphosphates were both very low. These results suggest that chiral phosphoantigens, as opposed to racemic mixtures, may have utility in immunotherapy.     

Changes in colonic myoelectric spiking activity during stimulation by bisacodyl

The purpose of this study was to determine some relationships between colonic myoelectric spiking activity and intraluminal propulsion when colonic peristalsis was stimulated by bisacodyl. Myoelectric recordings were obtained in 12 subjects by means of a 50 cm long Silastic tube equipped with four bipolar electrodes fixed at 10-cm intervals. The tube was introduced into the left colon by flexible sigmoidoscopy and the electrodes were located at 50, 40, 30, and 20 cm from the anal verge. A small polyethylene catheter opening at the proximal end of the Silastic tube was used for introducing the laxative into the colon. One hour recording sessions were obtained before and after bisacodyl administration (5 mL of 0.4% solution). The control tracings showed that colonic spiking activity was made of rhythmic stationary bursts that occurred at only one electrode site and of sporadic bursts that were either propagating over the whole colonic segment or nonpropagating. Administration of bisacodyl was followed by complete suppression of the rhythmic stationary activity; a considerable increase in the sporadic spiking activity, propagating as well as nonpropagating; the occurrence of abdominal cramps and urgency to defecate, both associated with the propagating sporadic spike bursts. It is concluded that colonic propulsion induced by bisacodyl may be dependent upon the production of the sporadic bursts, particularly the propagating ones, while the rhythmic stationary bursts do not seem to play a significant role in colonic transit.     

Plasma membrane folds on the mast cell surface and their relationship to secretory activity

Changes in the surface morphology of secreting mast cells have been followed by scanning electron microscopy. Mast cells isolated from the rat peritoneal cavity have folds of plasma membrane that form snake-like ridges on their surfaces. Fold length varies considerably from cell to cell, whereas fold width and depth appear to remain relatively constant. To assess the possible relationship between secretory activity and surface folding, a seimquantitative method was used for measuring fold length in control and secreting populations. A positive correlation is found between secretion of histamine and the extent of membrane folds on the mast cell surface. The source of the membrane required for fold formation is probably secretory granule membrane incorporated into the plasma membranene as a result of exocytosis. Furthermore, a distinct cell type devoid of surface folds, designated as a raspberry-type cell, is found to occur as an integral part of a normal population of mast cells. This cell type is resistant to stimulation by polymyxin.     

Changes in blood leucocyte populations induced by acute maximal and chronic submaximal exercise

Absolute (x 10(3).mm-3) or relative (%) numbers of blood leucocyte types (monocytes, lymphocytes, neutrophils) and lymphocyte subsets (T11+, T4+, T8+, B1+, and NKH1+) reacting with specific monoclonal antibodies were determined at rest, immediately after maximal exercise on a treadmill, in six controls (C), and in six young cyclists before training (BT) and after 5 months of training (AT). Maximal exercise significantly increased the absolute number (mobilization) of virtually all the types of leucocytes and subsets of lymphocytes in C, BT and AT subjects. In these subjects mobilization of natural killer cells (NKH1+) and cytotoxic/suppressor T lymphocytes (T8+) was greater than mobilization of the other leucocyte types and lymphocyte subsets; however, maximal exercise induced no significant changes in the relative numbers of any leucocyte types and lymphocyte subsets, except in the case of T4+ lymphocytes in At cyclists. Chronic submaximal exercise induced increased mobilization of neutrophils and decreased mobilization of lymphocytes during maximal exercise, except in the case of B lymphocytes (B1+) and NKH1+ cells, and decreases in the absolute and relative number of neutrophils at rest. It remains to be seen how these results can explain the modifications of leucocyte activities noted in vitro after isolated or chronic exercise.     

Movements and associations of ribosomal subunits in a secretory cell during growth inhibition by starvation

In Chironomus tentans salivary gland cells, the cytoplasm can be dissected into concentric zones situated at increasing distances from the nuclear envelope. After RNA labeling, the newly made ribosomal subunits are found in the cytoplasm mainly in the neighborhood of the nucleus with a gradient of increasing abundance towards the periphery of the cell. The gradient for the small subunit lasts for a few hours and disappears entirely after treatment with puromycin. The large subunit also forms a gradient but one which is only partially abolished by puromycin. The residual gradient which which is resistant to the addition of the drug is probably due to the binding of some large ribosomal units to the membranes of the endoplasmic reticulum (J.-E. Edstrom and u. Lonn. 1976. J. Cell Biol. 70:562-572, and U. Lonn and J.-E. Edstrom. 1976. J. Cell. Biol. 70:573-580). If growth is inhibited by starvation, only the puromycin-sensitive type gradient is observed for the large subunit, suggesting that the attachment of these newly made subunits to the endoplasmic reticulum membranes will not occur. If, on the other hand, the drug-resistant gradient is allowed to form in feeding animals, it is conserved during a subsequent starvation for longer periods than in control feeding animals. This observation provides a further support for an effect of starvation on the normal turnover of the large subunits associated with the endoplasmic reticulum. These results also indicate a considerable structural stability in the cytoplasm of these cells worth little or no gross redistribution of cytoplasmic structures over a period of at least 6 days.     

Unusual inhibition of monoamine oxidase activity induced by clorgyline

The phenomenology of inhibition of FAD-containing type A monoamine oxidase by clorgyline solutions containing negligibly small amounts of clorgyline that are insufficient for stoichiometric covalent blocking of a perceptible amount of the coenzyme was studied. The nature of this phenomenon consists in the fact that at monoamine oxidase concentrations of about 10(-8) M, more than 50% of the enzyme activity in inhibited by clorgyline (less than or equal to 10(-10) M), although is accordance with a well-defined mechanism after monoamine oxidase-catalyzed tautomerization clorgyline presumably interacts with FAD at a 1:1 stoichiometric ratio. This effect termed as secondary inhibition seems to be induced not by clorgyline proper, not by changes in the solvent induced by this compound. In other words, clorgyline may initiate the synthesis of a new hypothetical inhibitor (IIC) in aqueous media which causes a reversible inhibition of the same specific inhibitory site of the enzyme. This site is responsible for the initial binding of acetylene inhibitors and catalyzes the formation of their allenic derivatives.