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Biomedical subjects

R Peters

Publications and source records attributed to R Peters.

At least 253 records · Page 14Linked to original sources

Does community care for the mentally ill make a difference? A tale of two cities.

Matched groups of schizophrenic patients in Portland, Ore., and Vancouver, B.C., were compared approximately 1 year following discharge from an index hospitalization. Whereas Vancouver boasts a rich network of accessible private services and a public mental health system that provides a model of care for the chronically mentally ill, Portland's aftercare facilities at the time of the study were limited. One year after discharge the Vancouver cohort experienced fewer readmissions, was more apt to be employed, and reported a higher level of well-being, all of which suggest that community aftercare positively affects the negative symptoms of schizophrenia.

Adolescent↗

[Tissue distribution of iso-metronidazole and metronidazole in tumor-bearing C3H inbred mice].

Among the group of nitroimidazole radiosensitizers, predominantly misonidazole and metronidazole have so far been submitted to an extensive clinical testing. However, neurotoxic side effects have limited the dose of the substance necessary to obtain a maximal effect of sensibilization. Therefore, extensive efforts are being undertaken in the search for new compounds of equally good radiosensitizing action but with less side effects. One approach is to use substances of lower lipophilicity which will reduce penetration into the cerebral tissue. Proceeding from these considerations, comparative investigations were carried out with metronidazole (1-(2'-hydroxyethyl)-2-methyl-5-nitroimidazole) and iso-metronidazole (1-(2'-hydroxyethyl)-2-methyl-4-nitroimidazole), since in vitro but also in animal experiments the both substances showed an equally good radiosensitizing action while the lipophilicity of iso-metronidazole is much lower. Whereas for the metronidazole about the same distribution of the substance was found in all the organs investigated and also in the tissue of the mammary adenocarcinoma of C3H mice, the maximal concentration of iso-metronidazole in the cerebral tissue reached only about 50% of that in tumor tissue. This property, combined with the improved solubility, make the iso-metronidazole appear more appropriate for clinical testing than metronidazole.

Adenocarcinoma↗

Anion transport in single erythrocyte ghosts measured by fluorescence microphotolysis.

Fluorescence microphotolysis was used to measure in single resealed human erythrocyte ghosts the band 3-mediated transport of the fluorescent anion N-(7-nitrobenzofurazan-4-yl)-taurine (NBD-taurine). Transport was reduced to less than 5% of the control by the specific inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). The accuracy of the determination of the rate constant for NBD-taurine influx was approximately +/- 15% as calculated from repetitive measurements in individual ghosts. The sample population distribution of the rate constant was slightly skewed towards values larger than the mean. The rate of NBD-taurine transport showed an optimum near pH 7. The Arrhenius plot was linear in the range from 28.5 degrees C to 51 degrees C with an apparent activation enthalpy of 21.4 kcal/mol.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Nucleo-cytoplasmic flux and intracellular mobility in single hepatocytes measured by fluorescence microphotolysis.

Fluorescence microphotolysis was used to measure nucleocytoplasmic flux in single rat hepatocytes for a series of dextrans ranging in molecular mass from 3 to 150 kd. The cytoplasmic translational diffusion coefficient DC and the nucleoplasmic diffusion coefficient DN of a 62-kd dextran were also determined. DC was approximately 2 X 10(-8) and DN approximately 3 X 10(-8) cm2/s, i.e., 1/20-1/15 of the value in free solution. The mobile fraction amounted to 0.7-0.8 in measurements of both intracellular diffusion and nucleo-cytoplasmic flux. The flux of dextrans from cytoplasm to nucleus depended inversely on molecular mass with an exclusion limit between 17 and 41 kd suggesting that the nuclear envelope has functions of a molecular sieve. Employing the Pappenheimer-Renkin equations, a functional pore radius of 50-56 A was derived. By comparison with recent measurements on isolated liver cell nuclei, large quantitative differences between the intracellularly located and the isolated nucleus were revealed.

Animals↗

Flux measurement in single cells by fluorescence microphotolysis.

Fluorescence microphotolysis--widely employed for diffusion studies--can be used to measure transfer (flux) of fluorescent solutes through membranes in single cells and organelles. This article analyses the methodological basis of flux measurements, provides experimental tests, and discusses potential applications. The principle of the method is to equilibrate cells, organelles or vesicles with a fluorescent solute, to deplete the interior of individual cells etc. of fluorescein by the pulse of a high-intensity microbeam, and to monitor influx of solute by microfluorometry. Simple equations are given and a computer curve fitting program is described by which rate constants of influx and membrane permeability coefficients can be derived from fluorescence measurements. The permeability of individual "leaky" human erythrocyte ghosts to fluorescein-isothiocyanate-labelled bovine serum albumin has been measured under various conditions. Multiple exposure to the high-intensity microbeam had no effect on permeability within experimental error. Flux measurements have been also performed on individual vesicles of 1-2 micron radius which had been derived from ghosts. The potential application of the method to sub-lightmicroscopic vesicles and to organelles within living cells is discussed.

Erythrocyte Membrane↗

Recognition of the 'calcium paradox' and the effects of verapamil and gallopamil in human adenoidal mast cells.

Human mast cells from adenoids show when resuspended in medium containing 10(-3) M CaCl2 after their temporary exposure to Ca2+-free saline for about 20 min an irreversible reduction of responsiveness to a variety of stimuli: The histamine release induced by concanavalin A or ionophore A 23187 is only 30-50% of the one obtained in cells which were kept in 10(-3) M Ca2+ throughout the experiment. This phenomenon called 'calcium paradox' can be almost entirely avoided if the cells are temporarily exposed to 10(-4) M Ca2+ instead of Ca2+-free saline. Number yields, average histamine contents of mast cells and the rate of the spontaneous histamine release are not affected by the transitory lack of Ca2+, nor is the histamine release enhancing effect of adenosine. At 10(-3) M Ca2+ concentration the calcium antagonists verapamil or gallopamil cause a significant inhibition of the Con A-induced histamine release only at concentrations much higher (10(-4) M than those effective in smooth muscle preparations. The actions of both calcium antagonists were not affected by the presence of added extracellular adenosine.

Adenoids↗

The electrophysiologic effects of oral cibenzoline.

Five male patients with chronic stable ventricular arrhythmias underwent a placebo controlled ascending dose study with oral cibenzoline, a new type 1 antiarrhythmic drug. Ambulatory ECG (Holter) recordings and electrophysiologic studies were done while on placebo and on the maximum dose of cibenzoline. Drug toxicity, manifested by vomiting and QRS widening, accompanied by very high serum cibenzoline concentrations, was seen in two patients. A major reduction (greater than 85% in ventricular premature beats occurred in three patients including two in whom only relatively low serum concentrations had been achieved. Cibenzoline caused significant increases in AH (97 +/- 26 vs. 110 +/- 23 msec, p less than 0.01) and HV (59 +/- 7 vs. 78 +/- 7 msec, p less than 0.02), a major but statistically not significant increase in QRS (99 +/- 12 vs. 128 +/- 27 msec, NS) but QT (38 +/- 2 vs. 38 +/- msec) and QTc (42 +/- 1 vs. 44 +/- 3 msec) were essentially unchanged, even in toxic patients. Cibenzoline had no consistant effect on sinus cycle length, sinus node recovery time, or the relative, functional or effective refractory periods of the atrium and AV node. We conclude that cibenzoline has potent type 1 effects in prolonging HV but may be unique in not affecting QT or QTc, even at toxic levels. Its effects upon AH were unexpected and warrant further study.

Aged↗

Nuclear envelope permeability measured by fluorescence microphotolysis of single liver cell nuclei.

Fluorescence microphotolysis ("photobleaching") has been widely used to measure translational diffusion coefficients of lipids and proteins in cell membranes. This communication shows that fluorescence microphotolysis can be also employed for measurement of membrane transport in single cells and organelles. The influx of fluorescently labeled dextrans of graded molecular size into leaky human erythrocyte ghosts and isolated rat liver cell nuclei has been measured. For the nuclear envelope, a functional pore radius of 56-59 A is derived.

Animals↗

Translational diffusion in phospholipid monolayers measured by fluorescence microphotolysis.

A method is described that eliminates surface flow in monolayers at the air-water interface and makes possible diffusion measurements by fluorescence microphotolysis ("photobleaching"). In contrast to previous studies that did not account for surface flow, lipid probe diffusion has been found to be similar in densely packed monolayers and in related bilayers. Furthermore, it seems that lipid diffusion is based on the same molecular mechanism in monolayers, bilayers, and potentially also cell membranes. In monolayers of L-alpha-dilauroylphosphatidylcholine (Lau2-PtdCho) the translational diffusion coefficient D of the fluorescent lipid probe N-4-nitrobenzo-2-oxa-1,3 diazole egg phosphatidylethanolamine decreased from 110 microns2/s at a surface pressure II = 1 mN/m to 15 microns2/s at II = 38 mN/m (T = 21-22 degrees C). Data could be fitted by the "free volume model." In monolayers of L-alpha-dipalmitoylphosphatidylcholine (Pam2-PtdCho) D decreased by greater than 3 orders of magnitude upon increasing II at constant temperature, thus indicating a fluid-to-crystalline phase transition. In Lau2-PtdCho/Pam2-PtdCho monolayers phase separation has been visualized in the fluorescence microscope and the effect on D measured. These results suggest that monolayers are a promising model system for studying the molecular mobility of lipids and other cell membrane components.

Liposomes↗

Cigarette smoking and state-dependent memory.

Two experiments were carried out to investigate whether cigarette smoking could produce state-dependent learning (SDL) in humans. The first experiment was concerned with the methodological issue of choosing an appropriate control cigarette for use in an SDL design. A low nicotine content (0.2 mg) cigarette was chosen as it did not appear to affect the physiological arousal of the subjects. In Experiment 2, it was shown that cigarette smoking can produce state-dependent memory effects. The most likely basis for the results is the arousal produced by the nicotine content of the cigarette.

Adult↗

Lateral and rotational diffusion of bacteriorhodopsin in lipid bilayers: experimental test of the Saffman-Delbrück equations.

Lateral diffusion of bacteriorhodopsin and a lipid analogue has been measured in dimyristoylphosphatidylcholine bilayers as a function of temperature, phospholipid/protein (mol/mol; L/P) ratio, and aqueous phase viscosity. The protein lateral diffusion coefficients measured above the temperature at which the lipid gel-liquid/crystalline phase transition occurs (Tc) are combined with previously determined rotational diffusion coefficients to provide a test of the Saffman-Delbrück equations [Saffman, P. G. & Delbrück, M. (1975) Proc. Natl. Acad. Sci. USA 72, 3111-3113]. Insertion of the diffusion coefficients into these equations enables the protein diameter to be calculated. The value of 4.3 +/- 0.5 nm so obtained is in reasonable agreement with the known structure of bacteriorhodopsin. A 12-fold increase in the viscosity of the aqueous phase reduces protein lateral diffusion coefficients by 50%, which is also consistent with the Saffman-Delbrück equations. Both protein and lipid lateral diffusion coefficients decrease with decreasing L/P ratio above the Tc. It is argued that, at a high L/P ratio, this effect is probably due to changes in membrane viscosity while, at a low L/P ratio, "crowding" effects (steric restrictions) and protein aggregation become important. When comparing diffusion measurements made in different systems, it is important to take the effect of the L/P ratio into account. When this is done, other published measurements of freely diffusing membrane proteins are in good agreement with the present results and the predictions of the Saffman-Delbrück equations. Below the Tc, the presence of protein enhances diffusion rates. The overall effect is to smooth out the large change in diffusion coefficient that occurs at the Tc.

Bacteriorhodopsins↗