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Biomedical subjects

A C Jackson

Publications and source records attributed to A C Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Wave propagation, input impedance, and wall mechanics of the calf trachea from 16 to 1,600 Hz.

Propagation of waves in the airways is important in flow limitation as well as in oscillation mechanics. In five excised calf tracheae, we measured phase propagation velocity (c) and input impedance with open (Zop) or closed end (Zcl) for frequencies (f) between 16 and 1,600 Hz at two axial tensions [nonstretched (TN) and stretched (TS); TS > TN]. From 16 to 64 Hz, c slightly increased because of the viscoelastic properties of the wall tissues. Between 64 and 200 Hz, c was relatively constant and less than the free-field speed of sound (c0 = 340 m/s), with values smaller at TS (140 +/- 39 m/s) than at TN (172 +/- 35 m/s). Above 200 Hz, c exceeded c0 and displayed two maxima at approximately 300 and approximately 700 Hz, with values of approximately 360 and approximately 550 m/s, respectively. For f > 1,400 Hz, c approached c0. We provide evidence that the two maxima in c were the result of the two-compartment behavior of the wall tissues, i.e., the separate cartilaginous and soft tissues. A nonrigid tube model with its wall impedance composed of two series resistance, compliance, and inertance pathways in parallel simultaneously fits c, Zop, and Zcl well and hence provides a link among these data. By use of the relationship between volumetric wall parameters and the tracheal geometry, separate material properties such as viscosity and Young's modulus of both the soft tissue (approximately 1 cmH2O.s and approximately 0.26 x 10(4) cmH2O, respectively) and the cartilage (approximately 3.7 cmH2O.s and approximately 2 x 10(4) cmH2O, respectively) were estimated. These results indicate that measures of c and Zop or Zcl data over these frequencies provide information about the dynamic mechanical properties of both the soft tissue and cartilage in the airway walls.

Animals↗
PubMed1993

Large granular lymphoproliferative disease associated with nephrotic syndrome, renal failure and leukoencephalopathy.

A 23-year-old black female presented with general malaise, headache, high white cell count (136 x 10(9)/L), thrombocytopenia and nephrotic syndrome. She proved to have large granular lymphoproliferative disease with a natural killer cell phenotype and without a clonal rearrangement of the T-cell receptor genes. Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS). She developed a monophasic neurological illness, and rapidly became comatose six days after the initiation of high dose prednisone therapy. Computerized tomography of the brain showed marked hypodensity of the subcortical white matter. She regained consciousness subsequently, but died six months after her initial presentation with uncontrolled lymphocytosis and renal failure. Autopsy revealed FSGS with glomerular collapse and microcystic dilatation of the renal tubules, and there was perivascular demyelination in the subcortical white matter of the brain. We speculate that lymphokines released by the natural killer cells may have played an important role in the pathogenesis of both the nephrotic syndrome and leukoencephalopathy.

Acute Disease↗
PubMed1993

Cholinergic system in experimental rabies in mice.

A defect in cholinergic synaptic neurotransmission could explain the neuronal dysfunction that has been observed in rabies. The enzymatic activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and enolase were assessed in the brains of rabies virus strain CVS-infected and uninfected mice. No statistically significant differences in activities of ChAT, AChE, or enolase were observed in the cerebral cortex or hippocampus of moribund CVS-infected mice versus controls. Binding to muscarinic acetylcholine receptors, which was assessed with 3H-labelled quinuclidinyl benzylate (QNB), was also not significantly different in the cerebral cortex or hippocampus of CVS-infected mice and uninfected controls. The studies suggest that dysfunction of the cholinergic system is unlikely of fundamental importance in this mouse model of rabies.

Acetylcholinesterase↗
PubMed1992

Effects of post-mortem autolysis on the detection of rabies virus genomic RNA and mRNA in mouse brain by using in situ hybridization.

The effects of post-mortem autolysis were studied on the detection of rabies virus RNA in the brains of mice with experimental rabies by using in situ hybridization (ISH). The brains of CVS-infected mice were subjected to autolytic periods in situ of up to 72 h. ISH was performed with 3H-labelled RNA probes for rabies virus glycoprotein gene genomic RNA and mRNA. During the post-mortem period there was progressive loss of signals for genomic RNA and mRNA, which was greater for mRNA. ISH signals in perikarya also changed for genomic RNA from a multifocal to a diffuse distribution during the post-mortem period. Rabies virus antigen was better preserved during the autolytic period. Effects of the agonal state, degradation of RNA by ribonucleases, and diffusion of RNA out of cells prior to fixation could explain the loss of ISH signals in post-mortem tissues.

Animals↗
PubMed1992

Detection of rabies virus mRNA in mouse brain by using in situ hybridization with digoxigenin-labelled RNA probes.

A non-isotopic method of in situ hybridization (ISH) was developed for the detection of rabies virus RNA in paraffin-embedded tissues. Digoxigenin-labelled RNA probes for rabies virus glycoprotein mRNA were used. The method had good sensitivity and low backgrounds, and there was excellent cellular localization of signals. ISH wih digoxigenin-labelled probes was compared with ISH with 3H-labelled probes. This non-isotopic method of ISH is more convenient than the radiolabelled method, and it is quicker because a long autoradiographic exposure is not required.

Animals↗
PubMed1992

Basis of neurovirulence of avirulent rabies virus variant Av01 with stereotaxic brain inoculation in mice.

Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation.

Animals↗
PubMed1992

Confidence bounds on respiratory mechanical properties estimated from transfer versus input impedance in humans versus dogs.

Using parameters typical of a dog, we have shown that estimates for the parameters in the six-element model of Dubois et al. would be very unreliable if either input (Z(in)) or transfer (Ztr) data from only 2-32 Hz were fit. It has subsequently been shown that this model is not appropriate for human Z(in) from 2-320 Hz. However, several studies have continued to apply the model to human Ztr data from only 2-32 Hz. In this study a sensitivity analysis is used to determine whether and why the six-element model could be applicable to lower frequency (less than 64 Hz) Ztr data in humans, but not Z(in) data over any frequency range. We first predicted the joint parameter uncertainty bounds assuming a fit to either 2-32 Hz Z(in) or Ztr data created from literature based mean parameter values. Consistent with previous studies, we predicted that the estimates will be very unreliable if obtained from Z(in) data for humans or dogs, or from Ztr data from dogs. Surprisingly, however, the reliability of several parameter estimates from human Ztr data from only 2-32 Hz are reasonable. We next evaluated the variability in 2-64 Hz based Ztr parameter estimates by comparing experimental variability in two healthy human subjects (over 10 and 13 trials) to theoretical and Monte Carlo numerical predictions based on a single trial. Again, the Ztr parameters were reliable. A simulation study was used to describe the reasons for enhanced reliability when using human Ztr data. It is shown that this reliability is largely dependent on alveolar gas compressibility, Cg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Influence of bifurcations on forced oscillations in an airway model.

Forced oscillations is a technique to determine respiratory input impedance from small amplitude sinusoidal pressure excursions introduced at the airway opening. Models used to predict respiratory input impedance typically ignore the direct effect of bifurcations on the flow, and treat airway branches as individual straight tubes placed appropriately in parallel and series. The flow within the individual tubes is assumed equivalent to that which would occur in infinitely long tubes. In this study we examined the influence of bifurcations on impedance for conditions of the forced oscillatory technique. We measured input impedance using forced oscillations in straight tubes and in an anatomically-relevant, four generation physical model of a human airway network. The input impedance measured experimentally compared well to that obtained theoretically using model predictions. The predictive scheme was based on appropriate parallel and series combinations of theoretically computed individual tube impedances, which were computed from solutions to oscillatory flow of a compressible gas in an infinitely long rigid tube. The agreement between experimental measurements and predictions indicates that bifurcations play a relatively minor direct role on the flow impedance for conditions of the forced oscillations technique. These results are explained in terms of the small tidal volumes used, whereby the axial distance traveled by a fluid particle during an oscillation cycle is appreciably smaller than branch segment lengths. Accordingly, only a small fraction of fluid particles travel through the bifurcation region, and the remainder experience an environment approaching flow in an infinite straight tube. The relevance of the study to the prediction of impedances in the human lung during forced oscillations is discussed.

Airway Resistance↗
PubMed1992

Respiratory input impedance from 4 to 256 Hz in normals and chronic airflow obstruction: comparisons and correlations with spirometry.

Measurement of respiratory system input impedance (Zrs) by forced oscillation (FO) has generally been limited to frequencies less than or equal to 50 Hz, and correlations with spirometry have been variable. Using FO from 4 to 256 Hz in normals, Jackson and colleagues recently described a first acoustic antiresonance frequency (Far,1) at approximately 170 Hz. Using the same frequency range, we compared several Zrs spectral characteristics with spirometry in 12 chronic airflow obstruction (CAO) patients (range FEV1 0.8 to 2.0 L) and 10 matched controls. Compared with controls, patients had a higher first resonance frequency (Fr,1) (mean +/- SD = 15 +/- 5 versus 10 +/- 2 Hz, p less than 0.02) and a higher Far,1 (196 +/- 11 versus 172 +/- 13 Hz, p less than 0.0002). Good correlations occurred between % predicted FVC and the Far,1 (r = -0.81, p less than 0.0000), between FEV1/FVC and the reactance at 20 Hz (r = -0.6, p less than 0.003), between FEV1 and Far,1 (r = -0.74, p less than 0.0001). Because Far,1 may be affected by airway wall mechanical properties, the shift in Far,1 seen in these patients may be due to airway wall properties in CAO. We conclude that measurement of Zrs up to 256 Hz requires little patient cooperation and may be clinically useful. It can differentiate CAO patients from controls and correlates well with spirometry. The first acoustic antiresonance frequency may reflect airway mechanical properties and provide information not available from Zrs measured at lower frequencies.

Airway Resistance↗
PubMed1992

Acoustic rhinometry: effects of decongestants and posture on nasal patency.

To determine whether acoustic rhinometry can be used to detect changes in nasal patency caused by decongestants or posture, we studied 10 healthy volunteers. Maps of the effective cross-sectional area of the nasal cavity as a function of distance into the respiratory system were generated, and an index of nasal cavity volume was calculated in the right and left nostril of each subject. The volume index was reproducible in subjects. The mean of the intrasubject coefficients of variation was 7.9%. After administration of phenylephrine in the form of a nasal spray, the volume index increased in the right nostril from 29.8 +/- 3.6 to 40.9 +/- 4.4 cm3 (mean +/- SEM) (p less than 0.001) and in the left nostril from 26.3 +/- 2.1 to 38.0 +/- 3.0 cm3 (p less than 0.001). On another occasion in the same subjects, the volume index was determined before and 90 minutes after oral administration of 60 mg pseudoephedrine. The volume index for the sum of both nostrils increased from 56.7 +/- 4.7 to 65.1 +/- 5.2 cm3 (p less than 0.5). In another group of subjects, turning from the supine position to the right side caused right nasal volume to decrease from 29.3 +/- 4.4 to 19.5 +/- 3.6 cm3 (p less than 0.003) and the left nasal volume to increase from 20.9 +/- 2.8 to 25.5 +/- 3.2 cm3 (p less than 0.05). We conclude that acoustic rhinometry can provide a sensitive index of changes in nasal geometry.

Ephedrine↗
PubMed1991

Biological basis of rabies virus neurovirulence in mice: comparative pathogenesis study using the immunoperoxidase technique.

The CVS strain of fixed rabies virus causes acute, fatal encephalomyelitis in young adult ICR mice. Variant RV194-2, which was selected from CVS virus in cell culture with a neutralizing antiglycoprotein monoclonal antibody, has a single amino acid change in the glycoprotein. The infections caused by CVS virus and RV194-2 virus were compared in mice for 14 days postinoculation of 5 x 10(7) PFU into the right masseter muscle. All CVS virus-infected mice died (mean time to death, 7.9 days), compared with a mortality rate of 8.5% for RV194-2 virus-infected mice. RV194-2 virus spread to the ipsilateral trigeminal ganglion during the first 2 days postinoculation, and both viruses spread to the ipsilateral motor nucleus of the trigeminal nerve in the pons. Both viruses spread centrifugally and caused infection of bilateral trigeminal ganglia on day 3. The viruses spread throughout the central nervous system (CNS) at similar rates, but CVS virus infected many more neurons than did RV194-2 virus. Rabies virus antigen was observed in only occasional CNS neurons after day 6 of RV194-2 virus infection. By this time, CVS virus had caused severe widespread infection. In this model, virulence depends on improved efficiency of viral spread between CNS neurons rather than the rate of spread or topographical distribution of the infection.

Animals↗
PubMed1991

Detection of rabies virus genomic RNA and mRNA in mouse and human brains by using in situ hybridization.

Rabies virus RNA was detected in mouse and human brains by in situ hybridization. 3H-labeled single-stranded RNA probes were prepared which were specific for genomic RNA and mRNAs coding for the five rabies virus proteins (N, NS, M, G, and L). Paraffin-embedded brain tissues from human cases of rabies and mice experimentally infected with the challenge virus standard (CVS)-11 strain of rabies virus and street rabies virus were examined. In CVS-infected mice, genomic RNA had a multifocal distribution in the perikarya of infected neurons, perhaps reflecting concentration of genomic RNA in viral factories. The mRNAs were more abundant than genomic RNAs in CVS- and street virus-infected mouse brains and had a diffuse distribution in the perikarya. Similar amounts of signal were present in infected neurons for mRNAs coding for different rabies virus proteins. In brain tissues from human cases of rabies, genomic RNA was much more abundant than the mRNAs in infected neurons. This finding suggests either a relative block at the level of transcription or greater loss of mRNAs than of genomic RNA during the agonal period, postmortem interval, or prior to penetration of fixative during immersion fixation.

Animals↗
PubMed1991

Physiological basis for resonant frequencies in respiratory system impedances in dogs.

The lumped six-element model of the respiratory system proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) has often been used to analyze respiratory system impedance (Zrs) data. This model predicts a resonance (relative minimum in Zrs) at fr between 6 and 10 Hz and an antiresonance (relative maximum in Zrs) at far at higher frequencies (greater than 64 Hz). The far is due to the lumped tissue inertance (Iti) and the alveolar gas compression compliance (Cg). An fr and far have been recently reported in humans, but the far was shown to be not related to Iti and Cg, but instead it is the first acoustic antiresonance of the airways due to their axial dimensions). Zrs data to frequencies high enough to include the far have not been reported in dogs. In this study, we measured Zrs in dogs for frequencies between 5 and 320 Hz and found an fr at 7.5 +/- 1.6 Hz and two far at 97 +/- 13 and 231 +/- 27 Hz (far,1 and far,2, respectively). When breathing 80% He-20% O2, the fr shifted to 14 +/- 2 Hz, far,1 did not change (98 +/- 9 Hz), and far,2 increased to greater than 320 Hz. The behavior of fr and far,1 is consistent with the structure-function implied by the six-element model. However, the presence of an far,2 is not consistent with this model, because it is the airway acoustic antiresonance not represented in the model. These results indicate that, for frequencies that include the fr and far,1, the six-element model can be used to analyze Zrs data and reliable estimates of the model's parameters can be extracted by fitting the model to the data. However, more complex models must be used to analyze Zrs data that include far,2.

Airway Resistance↗
PubMed1991

Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters.

The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice (n = 24, 6 to 8 weeks old) and hamsters (n = 9, 90-110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extraneural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extraneural disease before major central nervous system disease developed.

Animals↗
PubMed1990

Improved frequency response of pneumotachometers by digital compensation.

To measure impedance one measures or estimates flow, which is commonly done by measuring the pressure drop across a pneumotachometer. The frequency response characteristics of standard pneumotachometer/pressure transducers (PPT) limit their use to relatively low frequencies. Also, the frequency response of PPTs has been reported to be "load" dependent. Thus, the frequency response characteristics measured under "no-load" conditions, which theoretically could be used to compensate subsequent measurements, may not be appropriate for measurements made under loaded conditions. Another method of measuring impedance exists which depends on a reference impedance element other than a pneumotachometer. In this method, an oscillatory flow signal with known amplitude is generated and used to force the system being tested. Unlike PPTs, this oscillatory flow generator (OFG) is a closed system that allows measurements to be made only during breath holding. Our objective was to determine whether the frequency response of a PPT could be compensated using measurements made under no-load conditions, such that it accurately measured an impedance load. The frequency response of the PPT under no-load conditions was measured by the OFG and used to compensate the output of the PPT in subsequent impedance measurements. The compensated PPT was used to measure the impedance of a mechanical structure and the impedances of four human subjects. The impedances of the mechanical structure and the subjects were also measured using the OFG.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1990

Effects of tidal volume and methacholine on low-frequency total respiratory impedance in dogs.

The frequency dependence of respiratory impedance (Zrs) from 0.125 to 4 Hz (Hantos et al., J. Appl. Physiol. 60: 123-132, 1986) may reflect inhomogeneous parallel time constants or the inherent viscoelastic properties of the respiratory tissues. However, studies on the lung alone or chest wall alone indicate that their impedance features are also dependent on the tidal volumes (VT) of the forced oscillations. The goals of this study were 1) to identify how total Zrs at lower frequencies measured with random noise (RN) compared with that measure with larger VT, 2) to identify how Zrs measured with RN is affected by bronchoconstriction, and 3) to identify the impact of using linear models for analyzing such data. We measured Zrs in six healthy dogs by use of a RN technique from 0.125 to 4 Hz or with a ventilator from 0.125 to 0.75 Hz with VT from 50 to 250 ml. Then methacholine was administered and the RN was repeated. Two linear models were fit to each separate set of data. Both models assume uniform airways leading to viscoelastic tissues. For healthy dogs, the respiratory resistance (Rrs) decreased with frequency, with most of the decrease occurring from 0.125 to 0.375 Hz. Significant VT dependence of Rrs was seen only at these lower frequencies, with Rrs higher as VT decreased. The respiratory compliance (Crs) was dependent on VT in a similar fashion at all frequencies, with Crs decreasing as VT decreased. Both linear models fit the data well at all VT, but the viscoelastic parameters of each model were very sensitive to VT. After methacholine, the minimum Rrs increased as did the total drop with frequency. Nevertheless the same models fit the data well, and both the airways and tissue parameters were altered after methacholine. We conclude that inferences based only on low-frequency Zrs data are problematic because of the effects of VT on such data (and subsequent linear modeling of it) and the apparent inability of such data to differentiate parallel inhomogeneities from normal viscoelastic properties of the respiratory tissues.

Airway Resistance↗
PubMed1990

Inability to separate airway from tissue properties by use of human respiratory input impedance.

Respiratory input impedance (Zrs) from 2.5 to 320 Hz displays a high-frequency resonance, the location of which depends on the density of the resident gas in the lungs (J. Appl. Physiol. 67: 2323-2330, 1989). A previously used six-element model has suggested that the resonance is due to alveolar gas compression (Cg) resonating with tissue inertance (Iti). However, the density dependence of the resonance indicates that is associated with the first airway acoustic resonance. The goal of this study was to determine whether unique properties for tissues and airways can be extracted from Zrs data by use of models that incorporate airway acoustic phenomena. We applied several models incorporating airway acoustics to the 2.5- to 320-Hz data from nine healthy adult humans during room air (RA) and 20% He-80% O2 (HeO2) breathing. A model consisting of a single open-ended rigid tube produced a resonance far sharper than that seen in the data. To dampen the resonance features, we used a model of multiple open-ended rigid tubes in parallel. This model fit the data very well for both RA and HeO2 but required fewer and longer tubes with HeO2. Another way to dampen the resonance was to use a single rigid tube terminated with an alveolar-tissue unit. This model also fit the data well, but the alveolar Cg estimates were far smaller than those expected based on the subject's thoracic gas volume. If Cg was fixed based on the thoracic gas volume, a large number of tubes were again required. These results along with additional simulations show that from input Zrs alone one cannot uniquely identify features indigenous to alveolar Cg or to the respiratory tissues.

Acoustics↗