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Biomedical subjects

D Nelson

Publications and source records attributed to D Nelson.

At least 289 records · Page 16Linked to original sources

Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells.

Monoclonal antibody directed against the transformation-related protein p53 was microinjected manually into the nuclei of quiescent Swiss 3T3 mouse cells. The cells were subsequently stimulated with 10% fetal calf serum. Microinjection of p53 antibody at or around the time of serum stimulation clearly inhibited the subsequent entry of Swiss 3T3 cells into the S phase of the cell cycle. p53 antibody had no effect on serum-stimulated DNA synthesis when it was microinjected 4 hr or later after serum stimulation. Monoclonal antibody to an unrelated antigen, Lyt-2.2, had no effect on serum-stimulated DNA synthesis regardless of the time it was microinjected. Under similar experimental conditions, p53 antibody had no effect on simian virus 40- or adenovirus 2-induced DNA synthesis. These experiments add strength to the suggestion that p53 is involved in the regulation of cell proliferation.

Adenoviruses, Human↗

Effects of conventional and high frequency jet ventilation on lung parenchyma.

Despite the increasing acceptance of high frequency jet ventilation (HFJV), very little work has been done to determine if lung damage results from its use. We performed an experimental study to compare the effects of conventional ventilation with those of HFJV on the lung parenchyma of anesthetized dogs. Thirteen animals were studied for periods ranging from 2-24 h. Using a double-lumen Carlen's endotracheal tube, each animals's lungs were ventilated simultaneously but independently, one with conventional ventilation, the other with HFJV. No gross or microscopic evidence of atelectasis or barotrauma was noted in either group. Less hyperaeration was seen in the majority of jet ventilated lungs compared to the conventionally ventilated. In no case did the jet ventilated side show more damage than the control. We concluded that it is possible to use HFJV for 24 h without apparent parenchymal lung damage. Reduced hyperaeration is identified as a possible advantage of HFJV over conventional methods.

Animals↗

Indirect fluorescent-antibody technique for serological diagnosis of La Crosse (California) virus infections.

A clinically relevant indirect fluorescent-antibody technique (IFA) was developed for the serological diagnosis of La Crosse virus infections. The IFA (67%) was as sensitive as the hemagglutination inhibition (58%) and neutralization (58%) tests in the detection of antibodies in acute-phase specimens. Immunoglobulin M antibodies were detected by the IFA test in 48% (11 of 23) of these specimens. Diagnostically significant increases in IFA titer were detected in 86% (19 of 22) of the paired samples. Antibodies were detectable in some patients 7 years after infection; however, the IFA test was not as sensitive as the other two tests in the detection of previous infections.

Child↗

Cerebral blood flow changes with diuretic therapy in elderly subjects with systolic hypertension.

It has been feared that lowering the blood pressure (BP) of elderly patients with systolic hypertension (SH) may compromise cerebral perfusion. To test this hypothesis, BP, cerebral blood flow (CBF), plasma renin activity (PRA), blood counts, urinary and serum electrolytes and other blood chemistries were measured in fifteen elderly patients (ages 61-76 years) with SH (systolic BP greater than 170 and diastolic BP less than 100 mmHg). Gray matter flow (Fg) was calculated from clearance curves of inhaled 133-Xenon. All subjects were studied while untreated, as well as during long-term treatment (average 15 weeks) with hydrochlorothiazide. BP fell during treatment from 186/90 to 160/86 while average Fg and cerebrovascular resistance (CVR) were not significantly changed. There was some suggestion, however, that in patients who became normotensive the CVR decreased (p less than 0.05) while in those who did not Fg fell (p less than 0.05). Cerebrovascular response to 5% CO2 inhalation was impaired during both the treated and untreated states. Individual changes in Fg and CVR did not correlate with changes in BP or with changes in PRA, electrolytes or other chemistries. In general, cautious, gradual reduction of BP with a thiazide diuretic in SH of the elderly seems not to impair cerebral perfusion, but individual differences exist and further studies are needed to characterize them.

Aged↗

Reduced vascular trauma after temporary occlusion with modified Biemer and Yasargil clips.

The Biemer and Yasargil microvascular clips that are currently available commercially can traumatize the vascular endothelium. In an effort to resolve this problem, both clip designs were structurally modified by changing the length, width, and surface of the clip blades in various ways. Also, the occlusion force of the clips was set at either 15 or 30 g. Studies on the carotid arteries of 140 rats showed a correlation between the structural and mechanical alterations of the clips and the degree of endothelial trauma produced by temporary occlusion for 1 hour. The most favorable results were obtained with a Biemer clip that had long, wide, smooth blades and an occluding force of 15 g.

Animals↗

The controlled delivery of thiopental and delayed cerebral revascularization.

Sodium thiopental was administered to 10 dogs following embolization of the middle cerebral artery. Its effect on the "grace period" for revascularization was investigated by performing embolectomies 6 hours later. We observed a striking reduction in the size of infarction in the animals treated with thiopental at moderate and prolonged dosage levels. The control animals treated with pentobarbital received less protection against ischemia although blood levels were similar to those of the experimental groups during the period of vascular occlusion.

Animals↗

Mutational alteration of membrane phospholipid composition and voltage-sensitive ion channel function in paramecium.

A behavioral mutant of Paramecium tetraurelia (baA) has been isolated that has an abnormal response when placed in solutions containing Ba2+. This mutant is shown here to have a dramatic alteration of the sphingolipid and phosphonolipid composition of its ciliary membrane. This biochemical defect is present in independently isolated alleles at baA locus and segregates in crosses with the behavioral phenotype. Electrophysiologically, the mutation reduces significantly conductance of both voltage-sensitive Ca2+ channels and voltage-sensitive K+ channels. When the mutant is grown in sterol-supplemented medium, its behavior, electrophysiological properties, and lipid composition are hardly distinguishable from wild type grown under similar conditions. This mutant then, provides strong evidence that membrane lipids significantly influence the function of the membrane molecules responsible for the generation of action potentials.

Animals↗

Net influx and efflux of 22Na in erythrocytes from normotensive offspring of patients with essential hypertension.

Fresh erythrocytes from 35 young normotensive individuals (20 males), the offspring of patients with essential hypertension (EH), and from 24 normotensive controls (14 males) were incubated at 37 degrees C in an isotonic buffer with 22Na. After 80 min, the net influx (net accumulation) of 22Na was not significantly different in either group, but after 140 min it was significantly higher (8.2%, p less than 0.01) in erythrocytes from male offspring as opposed to male controls. After both 80 and 140 min of incubation, the net influx of 22Na was significantly higher in males than in females in the respective groups. During a 60-minute period the net efflux of 22Na from preincubated (180 min) erythrocytes in 14 males in the offspring group was not significantly different from that found in 10 male controls. These findings could indicate that little differences exists in vitro between offspring and controls in the undirectional fluxes across the membrane. The difference between the male groups in the net influx after 140 min could indicate a higher Na content in the intracellular space in the offspring group, as assumption subsequently verified in a follow-up. The net influx of 22Na after 140 min was significantly correlated (R=0.58, p less than 0.05) to total plasma aldosterone male controls, but not in the offspring. No differences in the mean concentrations of total aldosterone, plasma and urinary electrolytes or in serum gamma glutamyl transferase were noted between offspring and controls. Abnormal cellular handling of sodium at least in the male offspring of patients with EH for at least two generations may be an important predisposing factor for EH.

Adult↗

Scanning electron microscopic and X-ray energy spectrographic analysis of the inner surface of human atherosclerotic carotid plaques.

Forty specimens of carotid plaque from 30 patients who had suffered cerebrovascular accidents and 10 asymptomatic control patients were examined by light and scanning electron microscopy (SEM). The SEM revealed the finely detailed surface characteristics of the plaque including cell deposits, endothelial damage, and exposed subendothelium. X-ray energy spectrography scans revealed that 7 specimens had calcium deposits. Presurgical treatment with dipyridamole and aspirin inhibited or substantially reduced thrombus formation.

Aspirin↗

Ionic channels of Paramecium: from genetics and electrophysiology to biochemistry.

This paper reviews the combined genetical, electrophysiological and biochemical analysis of excitation that has been carried out in Paramecium. Paramecium cells display graded Ca++ action potentials in response to a variety of stimuli. These action potentials regulate the orientation of the ciliary beat hence the cell's swimming behaviour. A large array of mutants displaying altered behaviour have been isolated and mapped to over 20 loci. Detailed electrophysiological analyses have been carried out on several classes of mutants revealing defects in specific ion channels in some cases. Mutants have proven very useful to analyze channel properties, to unravel interactions between channels and to discover the function of these channels in a variety of cellular processes. Some important channels are located in the ciliary membranes and cilia as well as ciliary membranes can now be purified in high purity and reasonable yield. These fractions have been used recently in a variety of biochemical approaches to gain insight into the molecular components of the excitation machinery. Specific alterations in some minor membrane proteins have been found in two mutants as well as a specific defect in sphingolipids in a third mutant. Those alterations had to be distinguished from large scale variations in membrane proteins and lipids that occur in this organism in response to modifications in growth conditions. Several other recent biochemical developments are reviewed and the advantages as well as the difficulties of the genetic approach to the molecular study of biological processes are discussed.

Animals↗

Segregation of rapidly acetylated histones into a chromatin fraction released from intact nuclei by the action of micrococcal nuclease.

It has been previously shown that micrococcal nuclease digestion and subsequent fractionation of hen oviduct nuclei generates fractions enriched (first supernatant fraction - 1SF) and depleted (second supernatant fraction - 2SF) in ovalbumin genes, while a third fraction, the pellet fraction, contains about the same level of this gene as whole chromatin (Bloom and Anderson (1978) Cell 15, 141-150). We have utilized this fractionation method in an attempt to assess the extent and kinetics of histone acetylation associated with chromatin from the 1SF, 2SF, and pellet fraction. Hepatoma Tissue Culture (HTC) cells were labelled for 30 minutes in vivo with 3H-acetate, nuclei isolated and the chromatin fractionated. The specific activity of the histones in the 1SF was slightly greater than that of the 2SF (1.2 to 1.6 fold difference) independent of the length of nuclease digestion. If the labelling period is followed by short (10 to 60 minute) treatment of the cells with sodium butyrate, the more rapidly as well as more extensively acetylated histones are also preferentially found in the 1SF. This is in part the result of segregation of chromatin particles into the 1SF as the histones associated with these particles become hyperacetylated. That is, the extent of histone acetylation regulates the distribution of chromatin in the 1SF, 2SF and pellet fraction.

Acetates↗

Reye's syndrome in three siblings. Association with type A influenza infection.

Reye's syndrome occurred simultaneously in three siblings. All had characteristic changes in liver histology ascertained by light and electron microscopy. The two patients with the most severe disease also had serum that caused marked stimulation of mitochondrial state 4 respiration in vitro. Histocompatibility locus antigen typing showed that no unique haplotypes were shared by all three children. There was no evidence of exposure to aflatoxins, pesticides, or other substances that have been previously postulated to be associated with Reye's syndrome. Influenza A/Brazil/11/78-like virus was isolated from one patient, and all three patients had a fourfold or greater rise in hemagglutination-inhibiting antibody to H1N1 influenza virus.

Antigens, Viral↗

Visually monitored postrotary nystagmus in seven autistic children.

Therapists who evaluate the sensorimotor functions of autistic children have become increasingly interested in monitoring their responses to vestibular stimulation. In this study, the duration of the nystagmus reflex is visually monitored and then measured by means of a stop-watch. Each of 7 autistic subjects received 18 sessions (36 trials) of horizontal semicircular canal stimulation during a period of 25 days. In each trial a graduated acceleration in a hand operated rotating chair preceded an abrupt stop, with a rapid deceleration from 180 degrees/second to 0 degree/second. Although subject option (intentional response) imposes limitations on the data interpretation, inspection of the nystagmus functions over time suggests the following: substantial trial-to-trial variability; substantial subject-to-subject variability; greater scores following trials to the subjects' left (the direction of the second trial in each session) than to the right (the direction of the first); and no evidence of consistent change for most subjects in nystagmus duration across the 36 trials. Implications for clinical evaluation of nystagmus are discussed.

Autistic Disorder↗

Aneurysm clip testing meter.

The force that a vascular clip exerts when it is applied to a vessel is a critical factor in its safe and proper use. Permanent occlusion effected in the obliteration of aneurysms requires clip closure forces great enough to resist sliping, yet low enough not to damage the neck of the aneurysm. The authors consider the need for a device that can readily measure clip closing forces just prior to pre-surgical sterilization (immediately prior to implantation), and an instrument that meets that need is presented.

Aneurysm↗

Biomechanics of vascular occlusion in neurosurgery.

Principle factors involved in effective vascular occlusion were identified and incorporated into a computer program designed to calculate the minimal occlusion force (MOF) in accordance with a modified version of Laplace's law. In vivo, the carotid arteries of 14 guinea pigs were occluded for one hour at an experimentally determined MOF or MOF + 50. A good correlation was found between the computed MOF and the experimentally determined MOF. Scanning electron microscopic (SEM) examination of the endothelium of the occluded vessels revealed extensive damage with forces greater than the MOF.

Animals↗