Calcium and ATP regulate the activity of a non-selective cation channel in a rat insulinoma cell line.

A calcium-activated non-selective cation channel was observed in isolated plasma membrane patches from an insulin-secreting cell line (CRI-Gl). The conductance of the channel was approximately 25 pS with identical (140 mM KCl) solutions on either side of the membrane. However, some rectification was observed (smaller outward current) when sodium ions were present extracellularly.

Characterization and use in immunoradiometric assay of monoclonal antibodies directed against human proinsulin.

Proinsulin in human serum is heterogenous. Existing assay methods do not distinguish between the various forms intermediate on the pathway of processing from proinsulin to insulin. We report the production of mouse monoclonal antibodies against human proinsulin with biosynthetic human proinsulin (produced by recombinant DNA technology) as immunogen.

Comparison of 12-hour and 24-hour sustained-release theophylline in outpatient management of asthma.

A once-daily sustained-release preparation of theophylline (Theo-24) was compared to a twice-daily (bid) preparation (Theo-Dur). Fourteen subjects with asthma requiring daily therapy with theophylline were evaluated in a 30-day prospective study. Pulmonary function and serum levels of theophylline were measured.

Evidence of beta cell dysfunction which does not lead on to diabetes: a study of identical twins of insulin dependent diabetics.

Ten non-diabetic identical twins of insulin dependent diabetics were studied to see whether they showed changes in insulin secretion. The twins were selected because more than 11 years had elapsed since the diagnosis of the diabetic twin and they were therefore unlikely to develop diabetes, and they had had islet cell antibodies. Despite similar glucose concentrations to the controls the twins had greater total immunoreactive insulin responses to both oral (mean 3280 (SD 699) versus 2338 (1110) pmol/dl at 180 minutes; p less than 0.

LTB4 mediated hypoxemia in guinea pigs: relationship to pulmonary and cardiovascular pathophysiology.

LTB4 is released in the presence of lung injury and may therefore play a role in the pathophysiology of the lung damage. We therefore, administered LTB4 as an I.V.

Ibuprofen prevents synthetic smoke-induced pulmonary edema.

Multiple potentially injurious agents are present in smoke but the importance of each of these agents in producing lung injury as well as the mechanisms by which the lung injury is produced are unknown. In order to study smoke inhalation injury, we developed a synthetic smoke composed of a carrier of hot carbon particles of known size to which a single known common toxic agent in smoke, in this case HCI, could be added. We then exposed rats to the smoke, assayed their blood for the metabolites of thromboxane and prostacyclin, and intervened shortly after smoke with the cyclooxygenase inhibitors indomethacin or ibuprofen to see if the resulting lung injury could be prevented.

Inhibition of a calcium-activated, non-selective cation channel, in a rat insulinoma cell line, by adenine derivatives.

The effects of adenosine and adenine nucleotides on a calcium-activated non-selective cation channel, present in the plasma membrane of an insulin-secreting cell line CRI-Gl were investigated. Single-channel currents were recorded from inside-out membrane patches and the adenine derivatives applied to the solution bathing the cytoplasmic aspect of the membrane surface. The activity of this channel is shown to be inhibited by all the derivatives tested.

Inspiratory-to-expiratory time ratio and alveolar ventilation during high-frequency ventilation in dogs.

It has been suggested that the increase in inspiratory flow rate caused by a decrease in the inspiratory-to-expiratory time ratio (I:E) at a constant tidal volume (VT) could increase the efficiency of ventilation in high-frequency ventilation (HFV). To test this hypothesis, we studied the effect of changing I:E from 1:1 to 1:4 on steady-state alveolar ventilation (VA) at a given VT and frequency (f) and at a constant mean lung volume (VL). In nine anesthetized, paralyzed, supine dogs, HFV was performed at 3, 6, and 9 Hz with a ventilator that delivered constant inspiratory and expiratory flow rates.

Effects of mean airway pressure on gas transport during high-frequency ventilation in dogs.

In 10 anesthetized, paralyzed, supine dogs, arterial blood gases and CO2 production (VCO2) were measured after 10-min runs of high-frequency ventilation (HFV) at three levels of mean airway pressure (Paw) (0, 5, and 10 cmH2O). HFV was delivered at frequencies (f) of 3, 6, and 9 Hz with a ventilator that generated known tidal volumes (VT) independent of respiratory system impedance. At each f, VT was adjusted at Paw of 0 cmH2O to obtain a eucapnia.

Response of pulmonary macrophages to hyperoxic pulmonary injury. Acquisition of surface fibronectin and fibrin/ogen and enhanced expression of a fibronectin receptor.

The in vivo acquisition of coagulation plasma proteins on the surface of pulmonary macrophages was studied in guinea pigs breathing 95% oxygen. Fibrin/ogen and fibronectin appeared rapidly and concurrently on the surfaces of macrophages in the bronchoalveolar lavage fluid, which was judged by immunohistologic examination and flow cytometry. Pulmonary macrophages showed a parallel increase in the expression of a surface fibronectin receptor.

Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin.

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin.

Five new insulin-producing cell lines with differing secretory properties.

Five cell lines have been derived from a rat transplantable islet cell tumour using two different methods. The lines differ in morphology and contain and release different amounts of insulin and glucagon (insulin content, 1-90 pmol/10(6) cells; insulin release, 6-250 pmol/10(6) cells per 24 h; glucagon content, less than 0.005-35 pmol/10(6) cells; glucagon release, less than 0.

Single channel recordings of potassium currents in an insulin-secreting cell line.

Using the patch-clamp technique we observed three distinct classes of K+ channels which were spontaneously active in excised 'inside-out' membrane patches from an insulin-secreting rat pancreatic islet cell line (CRI-G1). Two of these occurred infrequently, one with a conductance of approximately 7 pS, and the other a conductance of 220 pS. The activation of the 220 pS K+ channel was dependent upon the membrane voltage and was sensitive to the concentration of calcium ions at the cytoplasmic surface of the membrane.

Marijuana smoking as cause of reduction in single-breath carbon monoxide diffusing capacity.

To investigate the effects of chronic marijuana smoking on lung function, pulmonary function tests including single-breath carbon monoxide diffusing capacities were performed in 15 healthy women who smoked 1.7 +/- 1.4 (mean +/- SD) marijuana cigarettes per day for 235 +/- 135 days per year for a mean of 10.

A general dimensionless equation of gas transport by high-frequency ventilation.

To identify a general relationship between eucapnic oscillatory flow (Vosc) and frequency (f) in high-frequency ventilation (HFV), we searched the literature for eucapnic HFV data in different mammalian species. We found suitable results for rat, rabbit, monkey, dog, human, and horse, which we expressed in terms of two dimensionless variables, Q = Vosc/Va and F = f/(VA/VD), with VA the alveolar ventilation and VD the volume of the conducting airways. The experimental HFV data define the linear regression equation in Q = 0.

Pulmonary function in normal subjects and patients with sarcoidosis after bronchoalveolar lavage.

To determine if fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage impairs pulmonary function in normal subjects or those with sarcoidosis, we measured flow-volume loops, thoracic gas volume, and single breath carbon monoxide diffusing capacity before, one half hour and 24 hours after lavage. We studied 12 normal subjects; six underwent a large volume lavage (approximately 500 ml saline instilled), and six underwent a small volume lavage (approximately 175 ml). Five subjects with sarcoidosis also had a small volume lavage.

Post-receptor insulin resistance after diazoxide in non-insulin dependent diabetes.

Insulin binding to monocytes and the counterregulatory hormone response to intravenous insulin was determined in six normal subjects and eight patients with non-insulin dependent diabetes mellitus (NIDDM), before and after seven days treatment with oral diazoxide. In the normal subjects diazoxide had no effect on insulin binding or sensitivity. In the patients with NIDDM diazoxide caused resistance to intravenous insulin with no change in the counterregulatory hormone response or in insulin binding to account for this.

Chemical sympathectomy decreases alveolar hypoxic vasoconstriction in lambs but not in sheep.

We studied the role of the sympathetic nervous system in the augmented vasoconstrictor response of the newborn lamb, compared with the adult sheep, by producing a chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Seven lambs, age 4-16 days, and five sheep, age 2 yr, were anesthetized and intubated with a double-lumen endotracheal tube, allowing ventilation of one lung with O2 to maintain systemic oxygenation while the contralateral lung was ventilated with N2 as a hypoxic challenge. Distribution of perfusion to each lung was evaluated using positron scintigraphy after inferior vena caval injections of 13N, a positron-emitting isotope.

Relationship for gas transport during high-frequency ventilation in dogs.

Alveolar ventilation during high-frequency ventilation (HFV) was estimated from the washout of the positron-emitting isotope (nitrogen-13-labeled N2) from the lungs of anesthetized paralyzed supine dogs by use of a positron camera. HFV was delivered at a mean lung volume (VL) equal to the resting functional residual capacity with a ventilator that generated tidal volumes (VT) between 30 and 120 ml, independent of the animal's lung impedance, at frequencies (f) from 2 to 25 Hz, with constant inspiratory and expiratory flows and an inspiration-to-expiration time ratio of unity. Specific ventilation (SPV), which is equivalent to ventilation per unit of compartment volume, was found to follow closely the relation: SPV = 1.

The site and mechanism of oxygen sensing for the pulmonary vessels.

Lung vessels are unique in the body in that they react to hypoxia with constriction rather than dilatation. Whether this characteristic is inherent in the lung vessel or is due to an influence from a sensor in the surrounding lung parenchyma is not resolved. Recent data, however, showing that vascular hypoxia as well as airway hypoxia can produce pulmonary vasoconstriction and that the sensor for alveolar hypoxia is upstream in the precapillary vessels, allows but does not prove the precapillary pulmonary artery itself to be the O2 sensor.

The effect of glibenclamide administration on insulin sensitivity and insulin binding to monocytes in normal subjects.

Insulin sensitivity and insulin binding to monocytes were determined in seven normal subjects before and after one week's treatment with glibenclamide 2 mg three times daily. Glibenclamide administration produced a 60% increase in maximal specific insulin binding to monocytes. There was no effect on the blood glucose response to an intravenous bolus of insulin but fasting blood glucose was significantly elevated following glibenclamide treatment.

The sulphonylurea receptor may be an ATP-sensitive potassium channel.

The stimulation of insulin secretion from the beta cells of the islets of Langerhans appears to be mediated by a decrease in the cell-membrane potassium-ion permeability. Tolbutamide reduced K+ movement through an ATP-sensitive K+ channel in patches of plasma membrane from an insulin-producing cell line when applied to the external surface of the membrane. The effect occurred at concentrations which exist in the serum of patients treated with tolbutamide and which stimulate insulin secretion from islets of Langerhans in vitro.