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J Foreman

Publications and source records attributed to J Foreman.

At least 91 records · Page 5Linked to original sources

The effect of rapid cooling and culture on in vitro insulin release in cryopreserved rat islets of Langerhans.

It has been reported that isolated pancreatic islets are functionally viable following cryopreservation using fast cooling and that such conditions should be more efficient for the selective destruction of immunocompetent passenger lymphoid cells than techniques employing slow cooling. This study examines the effect of extended pre-freeze and post-thaw culture (72 hr) on the in vitro function of rapidly cooled (70 degrees C/min) rat islets of Langerhans. The viability of the islets was assessed by their ability to secrete insulin in response to stimulation by glucose and theophylline both statically during batch incubations and dynamically in a perifusion system. Extended tissue culture was found to be essential for the retention of insulin secretory function of rapidly cooled islets which showed slightly suppressed but comparable secretion indices compared with non-frozen cultured islets.

Animals↗

Three solutions for preservation of the rabbit heart at 0 degree C. A comparison with phosphorus-31 nuclear magnetic resonance spectroscopy.

Phosphorus-31 nuclear magnetic resonance has been used to measure changes in tissue adenosine triphosphate and pH that occur during hypothermic preservation of rabbit hearts. Three potential preservation solutions were studied: the St. Thomas' Hospital no. 1 cardioplegic solution, Bretschneider's HTP solution, and a solution originated in our laboratory, CP5, which we have previously studied in the rabbit heart with functional assessment by Langendorff perfusion. After being flushed with one of these solutions, each heart was stored at 0 degrees C for 12 hours, during which time it was subjected to repeated phosphorus-31 nuclear magnetic resonance scans. It was shown that adenosine triphosphate levels decayed more slowly with CP5 than with either of the other solutions or in the control experiments. Adenosine triphosphate decay was also slower with Bretschneider's HTP than with St. Thomas' Hospital solution, but pH was somewhat better maintained with Bretschneider's HTP than with either other solution or in the control hearts, although the pH did not decrease drastically in any group. CP5 was designed to prevent cell swelling and to reduce the uptake of calcium during storage, for which reasons it contains 30 mmol/L glucose and 0.1 mmol/L calcium. The potassium content is somewhat higher and the sodium and magnesium content somewhat lower than in St. Thomas' Hospital solution, with the objective of stabilizing intracellular concentrations of these ions during storage.

Adenosine Triphosphate↗

Perfusion of rabbit kidneys with solutions containing propane-1,2-diol.

Propane-1,2-diol (propylene glycol, PG) permeates more rapidly than glycerol, has a strong glass-forming tendency, and appears to have a low toxicity. It is therefore attractive as a potential cryoprotectant for renal preservation. In this paper we compared the effect on subsequent function, of exposing rabbit renal cortical slices to 1 M PG or glycerol in a range of vehicle solutions and we demonstrated a remarkably low toxicity of PG at this concentration. Rabbit kidneys were then perfused with solutions containing PG up to a maximum concentration of 3 M, after which the cryoprotectant was removed and the function of cortical slices prepared from the perfused kidneys was assessed. Marked differences in perfusion characteristics were found between PG and glycerol and between different vehicle solutions for PG, but the two most suitable perfusates, both containing about 100 mM mannitol, permitted normal function in slices prepared after removal of PG. These results indicate that, with an appropriate vehicle perfusate, exposure to PG up to a concentration of 3 mol/liter has remarkably little effect upon vascular resistance and the renal cortical functions measured.

Animals↗

Cystine and lysine transport in cultured human renal epithelial cells.

The transport of the amino acids, cystine and lysine, was studied in epithelial cell lines propagated from human kidney cortex. Cystine uptake data were reproducible in different cell lines and did not vary over several cell passages of an individual cell line. The transport of this disulfide amino acid was sodium-dependent with kinetic analysis showing one apparent Kt system of 0.09 mmol/L and Vmax of 0.054 mmol/L cell water/min. Studies of the kinetics of lysine transport, however, revealed two uptake systems with apparent high and low affinities with Kt of 0.14 mmol/L and 5 mmol/L and Vmax of 0.041 and 0.167 mmol/L cell water/min, respectively. Glutamate appeared to be the most potent inhibitor of cystine uptake by these cultured human renal cells and this interaction was competitive. Although cystine did not inhibit lysine uptake, arginine and ornithine were shown to be major inhibitors, thus providing evidence for the presence of a shared dibasic amino acid transport system.

Arginine↗

Optimization of a vehicle solution for the introduction and removal of glycerol with rabbit kidneys.

Previous studies with rabbit kidneys in our laboratories have used a plasma-like solution as the vehicle for the introduction and removal of glycerol. Other workers have usually employed high-potassium solutions. In this study we have assayed the function of rabbit renal cortical slices after incubation in a range of solutions, each of which contained 1 M glycerol, for 4 hr, followed by stepwise removal of the cryoprotectant. The functions measured were endogenous oxygen consumption, p-aminohippurate uptake, and the ability of the slices to accumulate potassium. Exposure to glycerol produced a considerable reduction of slice function, but, in the presence of glycerol, elevation of the potassium concentration was beneficial, whereas high concentrations of magnesium were detrimental. The optimum potassium concentration was 70-100 mM. Replacement of chloride by a range of anions of higher molecular weight was either without benefit (glycerophosphate) or detrimental (sulfate, citrate, and gluconate). Elevation of total osmolality from 300 to 400 mosmolal with glucose, mannitol, glycerophosphate, or Pipes reduced slice function, but when the same osmolality was achieved by raising the concentration of all the components of the solution in the same ratio, there was no significant loss of function. There was a weak optimum pH at ca. 7.0. These experiments led to the formulation of a bicarbonate-buffered perfusate containing 80 mM potassium and 17.5 g Haemaccel per liter, having a pH of 7.0 with 5% CO2 at 10 degrees C, and an osmolality of 400 mosmol/kg. This solution was used to preserve rabbit kidneys for 20 hr at 10 degrees C, by continuous perfusion, and was compared with our previous Haemaccel perfusate, HP5, which contained 4 mM K+, 111 mM mannitol, and had a pH of 7.4. The two solutions were equally effective.

Animals↗

Characteristics of cultured human renal cortical epithelia.

Nine human kidney epithelial cell lines, isolated from small biopsied material and from whole kidney, were propagated in both a hormonally defined medium and a medium supplemented with serum. At confluency, hemicysts or domes, typical of cultured epithelial cells, were formed by these cells. Monolayers had junctional complexes between cells and the presence of numerous microvilli on the cell surface. Parathyroid hormone markedly stimulated these cells to produce cyclic AMP. They also contained high levels of gamma-glutamyltranspeptidase, leucine aminopeptidase, and maltase, enzymes that are associated with the brush-border membrane of the proximal tubule. The cultured cells demonstrated the ability to transport amino acids and alpha-methylglucoside, a substrate actively transported only by the proximal tubule in the kidney. Based on these findings, the cultured cells reflected a number of characteristics associated with the proximal tubule. These renal epithelial cell lines may provide a useful model for studying various aspects of human renal physiology and biochemistry.

Adult↗

Stimulation of human fetuses with sound and vibration.

Forty pregnant women between 30 and 42 weeks' gestational age were studied to examine the effects of external sound and vibration on the fetal heart rate. A significant increase in the mean duration and amplitude of the first acceleration after sound stimulus was found when these values were compared with the control values. Conversely the mean time to the first acceleration in the control period was greater than that in the stimulated period. There was a significant increase in the mean duration of fetal heart rate accelerations, the mean amplitude of fetal heart rate accelerations, and the total time spent in accelerations up to 15 minutes after the sound stimulus as compared with the control period. There was no change in the number of accelerations following the sound stimulus compared to control. These data suggest that vibratory acoustic stimuli may influence patterns of fetal heart rate during human pregnancy.

Acoustic Stimulation↗

Nonsurgical management of obstructive aortic thrombosis complicated by renovascular hypertension in the neonate.

The use of umbilical artery catheters has become commonplace in the intensive care nursery and has facilitated management in the very ill newborn infant. Thrombotic complications associated with the use of such catheters may be as high as 30%. The successful, nonsurgical management of either complete or partial aortic thrombosis, associated with renovascular hypertension, is reported in three infants. Aggressive supportive medical management resulted in a satisfactory outcome in all three infants.

Aortic Valve Stenosis↗

Solutions for preservation of the heart at 0 degrees C.

Solutions developed for cardioplegia and myocardial protection during elective ischemic cardiac arrest have also been used for the storage of heart grafts at 0 degrees C. In this study we show that a solution based upon the principles established in renal preservation experiments gives superior preservation of rabbit hearts at 0 degrees C. The solution contained K+ 25 mmol/L, Mg++ 10 mmol/L, sufficient glucose to prevent fluid uptake during storage (30 mmol/L), and a low concentration of calcium (0.1 mmol/L). The complete omission of calcium was detrimental to function after prolonged storage.

Animals↗

Radioimmunoassay of nafarelin ([ 6-(3-(2-naphthyl)-D-alanine)]-luteinizing hormone-releasing hormone) in plasma or serum.

A procedure which is suitable for the radioimmunoassay (RIA) of nafarelin [( 6-(3-(2-naphthyl)-D-alanine)]-luteinizing hormone-releasing hormone) in plasma or serum at concentrations as low as 50 pg/ml is described. Antiserum was prepared by replacing the pyroglutamyl portion of nafarelin with glutaric acid, coupling the product to keyhole limpet hemocyanin, and immunizing rabbits with the resulting conjugate. At a dilution of 1:30,000 the binding was approximately 50%. The antibodies did not cross react with luteinizing hormone-releasing hormone. For RIA, 125I-labeled analyte was used as the tracer and charcoal was used to separate the free and the bound fractions. No purification of samples was required prior to RIA. Accuracy of the method was assessed by adding known quantities of nafarelin to nafarelin-free plasma and determining the ratio of measured to added analyte. Linear regression analysis for the concentration range 0.050-5.00 ng/ml yielded a regression equation of y = 1.01x - 0.066 and a correlation coefficient of 0.997. At 0.050 ng/ml the CV was 11.3% (interassay). Additional validation was obtained from an in vivo study in which [3H]nafarelin was administered to monkeys and plasma profiles were determined by RIA, by high-performance liquid chromatography (HPLC), and by an HPLC-radiochemical method. The results obtained by RIA agreed well with those obtained by the HPLC methods.

Animals↗

Nasal absorption of nafarelin acetate, the decapeptide [D-Nal(2)6)]LHRH, in rhesus monkeys. I.

Nafarelin acetate, [D-Nal(2)6]LHRH, a highly potent superagonist of luteinizing hormone-releasing hormone, was given intranasally to six female rhesus monkeys. Absorption was rapid and very reproducible, with peak levels occurring at 15-30 min and a bioavailability of approximately 2% relative to a subcutaneous dose. The nasal dose response was highly nonlinear. The nonlinearity was apparently associated with the absorption phase, since elimination profiles at all doses were similar.

Absorption↗

The effect of cooling and warming rate on cortical cell function of glycerolized rabbit kidneys.

Experiments previously reported (I.A. Jacobsen, D.E. Pegg, H. Starklint, J. Chemnitz, C.J. Hunt, P. Barfort, and M.P. Diaper, Cryobiology 19, 668, 1982) suggested that rabbit kidneys permeated with 2 M glycerol are least damaged during freezing and thawing if they are cooled very slowly (1 degree C/hr). Using similar techniques of glycerolization, cooling, storage at -80 degrees C, rewarming, and deglycerolization, active cell function in cortical tissue slices prepared from such kidneys has now been studied. Oxygen uptake, tissue K+/Na+ ratio after incubation, and slice/medium PAH ratio after incubation were measured. Kidneys cooled at 3.1 degree C/min and warmed at 4.2 degrees C/min gave poor results in the previous studies and the lowest levels of cell function in the present experiments. Kidneys cooled at 1 degree C/hr exhibited degrees of slice function that were dependent on warming rate: warming at 1 degree C/min was better than warming at either 1 degree C/hr or c.20 degrees C/min. These results refine the previously drawn conclusions, (loc cit) and indicate optimal cooling and warming rates for rabbit kidneys containing 2 M glycerol, in the region of 1 degree C/hr cooling and 1 degree C/min warming. These rates are much lower than have hitherto been used by others for any system. Some implications of these findings are discussed.

Animals↗

Preservation of ischemically injured canine kidneys by retrograde oxygen persufflation.

Canine kidneys were briefly perfused with Ross and Marshall's hypertonic citrate solution and stored at O C. This study concerns the effect, during such storage, of insufflating various gases via the renal vein and allowing the gas to escape through needle perforations of the renal surface. We were able to confirm the finding of Ross and Escott that kidneys that have suffered 30 min of warm ischemia prior to preservation, will, if oxygen is so "persufflated" during 24 hr storage, provide life-supporting function when subsequently auto-grafted. Moreover, we were able to extend the preservation period to 48 hr after 30 min warm ischemia, and to achieve 24-hr preservation after 60 min of warm ischemia. Oxygen was essential: our results suggest that air is less effective than pure oxygen, and we found inert gases to be completely ineffective. Uniformly high oxygen tensions were measured throughout the kidneys during storage, but we were unable to demonstrate any resynthesis of adenosine triphosphate and adenosine diphosphate. The mechanism responsible for the effectiveness of retrograde oxygen persufflation remains obscure.

Animals↗