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Biomedical subjects

D J Phillips

Publications and source records attributed to D J Phillips.

At least 145 records · Page 8Linked to original sources

Detection of carotid occlusive disease by ultrasonic imaging and pulsed Doppler spectrum analysis.

Ultrasonic imaging of the cervical carotid arteries by ultrasonic arteriography and duplex scanning combined with pulsed Doppler spectrum analysis were investigated in a series of patients undergoing arteriography. By using the ultrasonic image as a guide for precise placement of the pulsed Doppler sample volume, the characteristics of blood flow at points of interest in the carotid arteries could be determined. Audible analysis of the Doppler signal permitted correct diagnosis of 23 of 26 (88%) high-grade stenoses or occlusions with ultrasonic arteriography and 24 of 26 (92%) with duplex scanning. Spectrum analysis of Doppler signals obtained with the duplex scanner detected all of the 22 high-grade stenoses. Spectral abnormalities of a lesser degree also were detected in 18 of 23 vessels (78%) with atherosclerotic plaques which should not have reduced cerebral blood flow. These techniques permit the accurate detection of and the distinction between high-grade stenoses and occlusion, as well as the identification of many plaques which are not large enough to affect intracranial hemodynamics.

Arterial Occlusive Diseases↗

Antiserums for immunofluorescent enumeration of human T lymphocytes utilizing fluoresceinated staphylococcal protein A.

Five lots (100 ml or more) of heterologous antiserums specific for human T lymphocytes were prepared using human or Rhesus monkey thymocytes as immunogens. After appropriate adsorptions, these antiserums reacted by immunofluorescence with 68% of human peripheral blood mononuclear cells and 98% of human thymocytes, with E-rosette--positive cells but not with EAC-rosette--positive cells or five human B-lymphoblastoid-cell lines. Blocking experiments showed that Rhesus monkey thymocytes share thymic antigenic determinant(s) with humans. E-rosette receptors modulated independently from T-cell heteroantigens. Non-E--rosetting neoplastic T cells were identified in several patients with lymphoproliferative malignancies. Applying both the E-rosette assay and the anti-T-cell serum provides a better method of defining the biologic properties of normal and neoplastic T lymphocytes. Standardization of immunofluorescent conjugates for human T- or B-cell enumeration is simplified if large lots of well-characterized antiserums are available.

Animals↗

The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells. II. Identification as a K cell.

Studies were carried out to determine whether the mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity (ADCC) to herpes simplex virus (HSV)-infected target cells has surface Fc receptors which participate in the reaction. The F (ab')2 fragment of human IgG antibody was inactive both in ADCC and in complement-mediated cytolysis, but retained the capacity to neutralize infectious virus, to agglutinate erythrocytes coated with viral antigens, and to bind to the surface of virus-infected cells. Treatment of sensitized virus-infected target cells with staphylococcus protein A, which has affinity for the Fc epitope of IgG, strongly reduced their susceptibility to lysis by ADCC in a dose-dependent relationship. These findings indicate that the Fc portion of IgG antibody to the virus is necessary for cytotoxicity. Treatment of blood mononuclear cells with either heat-aggregated gamma-globulin or HSV immune complexes inhibited effector cell activity. The presence of "third party" cellular immune complexes also strongly inhibited ADCC. Adsorption of mononuclear cells to plastic surfaces coated with soluble third party immune complexes resulted in a significant reduction in effector cell activity. These findings demonstrate that the ADCC effector cell possesses surface Fc receptors which are utilized in the ADCC reaction. The presence of Fc receptors on the surface of the effector cell indicates that it is a K cell rather than a null cell.

Antibodies, Viral↗

Correlation of structural transitions in coliphage R17 with its loss of infectivity.

A circular dichroism comparative study of isolated and in situ phage R17 RNA reveals in both cases the same degree of base pairing. However, thermal circular dichroism melting profiles exhibit the presence of free energy of interaction between RNA and capsid protein. It is apparent that the capsid stabilizes the RNA structure with and without the addition of Mg2+. A close RNA capsid association is also derived from pH titration circular dichroism studies. The pH melting of the RNA in situ starts to occur about 0-5 pH unit higher with and without the addition of Mg2+ than the acid denaturation of isolated RNA. A direct correlation between bathochromic CD peak shift to the main position band and loss of survivors is noted for the thermal melting as well as pH titration experiments. It is suggested that the heat and pH induced conformational alterations of R17 RNA in situ coinciding with loss of infectivity occur after an in situ alteration of nucleic acid-capsid protein interaction.

Capsid↗

Analysis of mononuclear cell surfaces with fluoresceinated staphylococcal protein A complexed with IgG antibody of heat-aggregated gamma-globulin.

Fluorescein-conjugated staphylococcal protein A (SPA) was complexed with either: 1) heat-aggregated IgG, 2) B cell specific antibody, or 3) T cell specific antibody and then used for an immunofluorescent analysis of mononuclear cell surfaces. Cellular Fc receptors failed to recognize the Fc region of aggregated IgG that had been blocked by SPA. Moreover, fluoresceinated SPA that had been complexed either with anti-Fab (B-cell specific) or T cell-specific antisera prevented the nonspecific binding of these reagents to the IgG-Fc receptors on mononuclear cells, thereby permitting the latter to be properly identified as B or T lymphocytes. In addition, when unconjugated SPA was added to presensitized target cells in a test for antibody-dependent cell-mediated cytotoxicity, cytolysis was abrogated.

Animals↗

The specificity of fetal IgM: antibody or anti-antibody?

Reference materials were produced to standardize the immunoglobulin class specificity and potency of immunofluorescent anti-IgM conjugates used for diagnostic tests for congenital syphilis. In attempting to mimic essential immunologic characteristics of syphilitic and nonsyphilitic infant sera, we evaluated these sera in comparison with processed adult sera. We were quite surprised to discover that some syphilitic babies do not produce significant quantities to IgM antibody to T. pallidum in response to their infection, as would be expected; instead, they make relatively large amounts of IgM anti-IgG. We found this to be true also for newborns and infants infected with cytomegalovirus, rubella, and toxoplasmosis. To our knowledge, this observation has not been previously reported. However, it could have been predicted from the knowledge that older infants and young children normally produce IgM antibodies to maternal IgG allotypes (Gm factors). We are disturbed that these findings suggest that currently recommended indirect immunofluorescence IgM tests for perinatal infection may not be disease specific. Our observations may be important for a better understanding of basic immunologic mechanisms of fetal-maternal to tolerance and fetal response to life-threatening infection.

Adsorption↗

Empirical findings relating sample volume size to diagnostic accuracy in pulsed Doppler cerebrovascular studies.

Ultrasonic duplex scanning has a sensitivity of 97% in detecting disease of the carotid bulb. However, the specificity is much less, being 37%. The error in distinguishing normal arteries from those with minimal disease appears to be in part related to the size of the sample volume of the pulsed Doppler. This paper addresses the importance of the features of scan head design in relation to distinguishing normal and diseased arteries.

Blood Flow Velocity↗

Organochlorine chemicals in human breast milk in Hong Kong.

The results of a small-scale survey of organochlorine contaminants in human breast milk are presented and compared to previous data from 1976 for Hong Kong, and to reported data from elsewhere. Concentrations of p,p DDT, dieldrin and hexachlorobenzene (HCB) in recent breast milk samples were slightly but significantly lower than those in samples taken a decade previously in Hong Kong. However, levels of gamma-HCH (hexachlorocyclohexane) were higher in the more recent samples. The concentrations of DDT, DDE and beta-HCH in Hong Kong breast milk remain among the highest reported in the literature. Probable routes of uptake of such contaminants include the ingestion of seafood, as these same compounds have previously been found at high concentrations in mussels from Hong Kong waters. Data for organochlorine levels in breast milk from other parts of Asia are not available, but trends in global pesticide usage suggest that significant contamination elsewhere in the continent is likely.

Adult↗

Flow velocity patterns in the carotid bifurcations of young, presumed normal subjects.

Spectral analysis of pulsed Doppler velocity waveforms has been found useful as a diagnostic technique in the assessment of carotid artery disease. While spectral broadening of the velocity waveform obtained at center stream sites is usually associated with arterial disease, the present study describes spectral patterns resulting from disturbed blood flow in the proximal branches of the carotid bifurcation in young, presumed normal human subjects. In those studied, spectral patterns in the bifurcation region exhibit characteristics similar to those occurring in zones of flow separation in model studies under conditions of steady flow. It is important to distinguish the spectral patterns due to arterial disease from those occurring in the normal bifurcation. This paper describes the types of flow disturbances noted in presumed normal arteries and points out the need to understand the flow velocity patterns that may be found at specific anatomical sites across the carotid bifurcation.

Adult↗

Evaluating carotid artery disease. The concordance between pulsed Doppler/spectrum analysis and angiography.

The results of ultrasonic pulsed Doppler duplex scanning with spectral analysis and computer pattern recognition are compared with the results of contrast arteriography in patients screened for extracranial carotid artery disease. The intraangiographer variability (one radiologist reading the same films twice) and the interangiographer variability (two radiologists reading the same film independently) were also studied. To calculate degrees of agreement corrected for chance, the Kappa statistic was computed for all the evaluation methods employed. At the present time, the concordance between spectral analysis and cerebral contrast angiography reaches a Kappa value of 0.682 +/- 0.064. This level of agreement compares favorably with the interangiographer agreement level (K = 0.568 +/- 0.058) and the intraangiographer agreement (K = 0.711 +/- 0.054). The computer pattern recognition program predicted the degree of stenosis by angiography with an agreement of K = 0.721 +/- 0.059. This concordance compares favorably to that observed when the radiologists are compared with themselves and is greater than that reached by two different radiologists. The continuous improvement in precision and accuracy of duplex scanning offers the promise of its usefulness in clinical and epidemiological studies.

Blood Flow Velocity↗

Post-endarterectomy carotid ultrasonic duplex scanning concordance with contrast angiography.

The results of ultrasonic duplex scanning combined with spectral analysis are compared with the results of contrast angiography in patients after endarterectomy in which recurrence of carotid arterial disease was suspected. Thirty-six patients underwent a duplex scan study within 3 months of their post-operative angiogram, performed at their physician's discretion (44 studies). The overall accuracy of the method was 80%. Our ability to predict a greater than 50% diameter reduction along with total occlusion was 94%. The measure of agreement corrected for chance between arteriography and duplex scanning as expressed by the Kappa statistic was 0.675 +/- SE (K) 0.096. This level of agreement compared favorably to that of inter- and intra-observer variability in reading cerebral angiograms. The accuracy reported justifies the clinical use of ultrasonic duplex scanning in the detection of recurrent stenosis after carotid endarterectomy.

Blood Flow Velocity↗

Computer based pattern recognition of carotid artery Doppler signals for disease classification: prospective validation.

A computer based pattern recognition method has been developed to classify the percent diameter reduction in nonoccluded internal carotid arteries. Using a combined B-mode/pulsed Doppler unit, the system utilizes spectral waveforms obtained from the low common and proximal internal carotid artery locations. The ECG-R wave is used as a time reference to synchronize the averaging of Doppler spectra from 20 heart cycles. An averaged waveform is generated and represents the spectral data from which features are extracted for analysis. A stepwise selection algorithm identifies a feature subset for partitioning the entire range of disease into two states, less than and greater than a decision point. Three such partitions are made, leading to the following categories: Normal, 1-20, 21-50 and 51-99% dia. reduction. A classifier was trained, tested prospectively against unknown data and the results compared to angiography. Of the 170 vessels tested, 141 (82%) were classified in the same category by angiography and the computer system. Agreement for each category was 93% (27/29) for the normals, 81.5% (44/54) for the 1-20% lesions, 78% (29/37) for the 21-50% lesions and 82% (41/50) for the 51-99% lesions. The computer method and angiography differed by more than one category in only one of the 170 tests. The level of agreement corrected for chance (Kappa +/- SE(K] was 0.769 +/- 0.039. Future efforts will be directed toward dividing classification of disease further (especially in the 51-99% category), developing a dedicated microprocessor for on-line analysis of the signals and using the system for prospective epidemiological studies of various populations.

Adult↗