Showing papers in "Scopus in 1977"

Nuclear matrix: Isolation and characterization of a framework structure from rat liver nuclei

Abstract: A nuclear framework structure termed the nuclear matrix has been isolated and characterized. This matrix forms the major residual structure of isolated nuclei and consists largely of protein with smaller amounts of RNA, DNA, carbohydrate, and phospholipid. The nuclear matrix can be further resolved by combined treatment with DNase and RNase. The remaining nuclear protein structure, after extraction of 90 percent of the nuclear protein, 99.9 percent of the DNA, and 98 percent of the RNA and phospholipid, is termed the nuclear protein matrix. Electron microscopy of this final nuclear protein matrix reveals an interior framework structure composed of residual nucleolar structures associated with a granular and fibrous internal matrix structure. The internal matrix framework is derived from the interchromatinic structures of the nucleus, and is connected to a surrounding residual nuclear envelope layer containing residual nuclear pore complex structures. Sodium dodecyl sulfate-acrylamide gel electrophoresis of the nuclear matrix proteins demonstrates three major polypeptide fractions, P-1, P-2, and P-3, with average molecular weights of approximately 69,000, 66,000 and 62,000, as well as several minor polypeptides which migrate at approximately 50,000 and at higher molecular weights (>100,000). Polypeptides with molecular weights identical to those of P-1, P-2 and P-3 are also components of isolated nuclear envelopes and nucleoli, whereas isolated chromatin contains no detectable matrix polypeptides. This suggests that the major matrix polypeptides are localized in specific structural regions of the nucleus, i.e., nuclear envelope, nucleoli, and interchromatinic structures. The presence of cytochrome oxidase activity in the isolated nuclear matrix indicates that at least some integral proteins of the nuclear membrane are associated with the matrix.

Experimental cerebral concussion: Part 1. An electron microscopic study

Abstract: Cerebral concussion was produced in rats by an iron pendulum hitting the external occipital protuberance. This resulted in loss of consciousness lasting from 3 to 10 minutes with prompt recovery and no focal neurological signs. The energy absorbed by the head at the impact was calculated to be about 1450 gm/cm. Light microscopic survey showed only minor pathological changes. However, electron microscopic observation revealed considerable alteration which began at 30 minutes, reached a peak at 1 hour, and disappeared at 24 hours after concussion. The salient changes included severe swelling of the neuronal mitochondria at the point of impact (occipital cortex), and extracellular edema at the site of contre coup (frontal lobe). Topographically, the most severe alteration was seen in structures at the craniospinal junction (medulla oblongata and upper cervical cord), consisting of both mitochondrial and edematous changes. Although there was no visible opening of the capillary interendothelial junctions, extravasated ferritin particles were accumulated in the edematous regions, indicating a transient increase in the permeability of the blood-brain barrier.

Ultrastructural and biochemical evidence for a steroid containing secretory organelle in the perfused cat adrenal gland

Abstract: A correlative study of the ultrastructural and biochemical effects of ACTH on fasciculata cells was carried out on the isolated cat adrenal gland perfused in situ with Locke's solution. The outstanding morphologic feature of cortical cells exposed to microunit ACTH concentrations for 40 min was the abundance of electron-dense granules (0.2-0.4 mum). These organelles were observed in small groups in close proximity to the Golgi region and to the cell membrane. Morphometric and biochemical analysis of control and ACTH-treated glands demonstrated that ACTH stimulation was associated with a fourfold increase in the number of these granules and a comparable increase in the corticosteroid content of the gland. By contrast, ACTH failed to augment cortical lysosomal enzyme activity. These findings, which link steroid release to the appearance of intracellular granules, extend further the parallels between the mechanism of release of newly synthesized steroid and the release of preformed hormones stored in secretory organelles. These results also lend support to the concept that a process related to exocytosis may be the underlying mechanism for extruding steroid from the cortical cell.

Tissue persistence of gentamicin in man

Abstract: A two-compartment pharmacokinetic model was used to characterize serum concentrations and to predict tissue accumulation of gentamicin in 47 treated patients. Postmortem tissues were obtained in six cases; in each instance, tissues yielded the predicted amount of drug. Slow release of tissue-bound gentamicin accounts for its prolonged retention in the body. The two-compartment model adequately predicts gentamicin accumulation from serum concentrations and explains why this antibiotic persists in serum and urine. ( JAMA 238:327-329, 1977)

Comparative pharmacokinetics of coumarin anticoagulants XXX: relationship between total clearance and serum protein binding of dicumarol in rats

Abstract: The effect of serum protein binding on the elimination kinetics of dicumarol was studied. The serum free fraction of dicumarol was essentially independent of concentration over a wide concentration range and ranged from 0.00015 to 0.00079 in 10 adult rats. The total clearance of dicumarol in these animals ranged from 3.93 to 14.5 ml/kg/hr. As in previous studies, there was an excellent linear correlation between the elimination rate constant for dicumarol and the fraction of dicumarol in the liver (i.e., the amount of drug in the liver divided by the amount of drug in the body). Consistent with theoretical considerations, there was a positive and apparently linear relationship between the total clearance and the serum free fraction of dicumarol. The individual serum free fraction and the fraction in liver values for dicumarol were strongly correlated. The pharmacokinetic model based on a proportional relationship between the apparent elimination rate constant and the fraction in the liver applies to dicumarol but not to warfarin and has limited utility. On the other hand, the model relating total clearance to the serum free fraction has been found to apply to dicumarol, warfarin, and other extensively plasma protein-bound drugs and can be utilized under clinical conditions.

Comparative pharmacokinetics of coumarin anticoagulants XXXI: Effect of plasma protein on distribution kinetics of dicumarol in rats

Abstract: The purpose of this investigation was to determine, with respect to dicumarol, the effect of plasma protein binding on the pharmacokinetic parameters used conventionally to describe the distribution kinetics of a drug on the basis of the time course of its plasma concentration. After rapid intravenous injection, plasma dicumarol concentrations in adult male Sprague-Dawley rats declined triexponentially, with the terminal exponential phase starting at about 4 hr. The free fraction f, of dicumarol in the serum of individual animals ranged from 0.000150 to 0.000790. The parameters of the equation Ct = Pe-pit + Ae-alphat + Be-betat for plasma concentration Ct at time t were obtained by nonlinear least-squares computer fitting of the experimental data and varied appreciably between animals. Of these parameters, only beta showed a significant correlation with f. These observations indicate that the distribution kinetics of this very extensively plasma protein-bound drug, as reflected by the time course of its plasma concentration after intravenous injection, are apparently not affected by intersubject differences in plasma protein binding. There is a remarkable similarity in the valves of P, A, B, pi, and alpha for dicumarol and warfarin, even though the serum free fraction of these drugs differs considerably.

Intravenous theophylline therapy: nomogram guidelines

Abstract: We evolved a nomogram for guiding and standardizing intravenous theophylline therapy in hospitalized patients. It provides rapid calculation of a loading dose based on body weight and prev...

Stereographic projections of experimental electron density distributions

Abstract: The determination of electron density distributions in solids by X-ray (and neutron) diffraction has been applied to many different types of solids (for a survey see Coppens, 1975; Coppens and Stevens, 1977). Although several ways of illustrating the results are known (Smith and Absar, 1977), it is most common to display contour plots of the density distribution in planar sections through the molecule. However, significant features above and below a plane may easily be missed with this technique, and even when many sections are plotted the relative position of different density features and their possible chemical significance is not easily understood. A useful alternative is to display the charge density on the surface of a sphere about a point in stereographic projection (Fig. 1). The density on a spherical surface is projected on to a plane, and appears as if viewed from the opposite side of the sphere. Stereographic projections are described in detail in several texts (Azfiroff, 1968; Nuffield, 1966). Stereographic projections of the electron density are of particular value in revealing both the hybridization of atoms with lone-pair density and the orientation of the lone-pair peaks with respect to hydrogen bonds or neighboring ions. Also, the relationship of the crystal field to the location of density peaks from the partially filled d shell of transition metal atoms can be effectively displayed in a stereographic projection. Electron density distributions in stereographic projection have been presented by Stevens and co-workers (1976) showing the lone-pair density about some oxygen atoms, and by Rees and Mitschler (1976) showing the