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Biomedical subjects

D J Phillips

Publications and source records attributed to D J Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of monoclonal antibodies having specificity for human IgG subclasses: results of the 2nd IUIS/WHO collaborative study.

Following the 1st IUIS/WHO Collaborative Study of monoclonal anti-IgG subclass antibodies, a panel of WHO Specificity Reference Reagents (SRR) was established [Jefferis, R., et al. (1985) Immunol. Lett., 10, 223]. At the time, the hope was expressed that further reagents particularly for IgG2, and other allotypic specificities would become available which could be applied in a wide range of assay protocols. The 2nd study reports the evaluation of nineteen anti-subclass and seven anti-allotype monoclonal antibodies. The anti-IgG1 antibody HP6187 was equivalent in performance to the SRR. Others, that were not of the mouse IgG1 isotype, may be useful for particular applications. The anti-IgG2 antibody HP6200 could be a valuable addition to the WHO SRR; it is specific for an epitope in the Fab region but does not have the light chain bias of HP6014. Antibodies of putative allotype specificity exhibited the claimed specificity when used within protocols similar to those employed by the originating laboratory. It appears to be inherent in the nature of the epitopes (allotopes) recognized that it will take several years before reagents applicable to a wide range of techniques will become available.

Antibodies, Anti-Idiotypic↗
PubMed1992

Flow separation in the carotid bulb: prognostic significance.

It has been previously shown that boundary layer or flow separation occurring in the carotid bulb and detected by duplex scanning denotes minimal or no carotid atherosclerotic disease as demonstrated by angiography and reliably predicts aetiology other than carotid artery disease in symptomatic patients. To evaluate outcome at long-term follow-up we prospectively studied 94 patients (48 males, 46 females) who demonstrated bilateral flow separation. Mean age was 61.2 years (27 to 86 years). Mean follow-up was 57 months (5 to 113 months). There was one death during follow-up at 69 months. It was stroke related. Using age and sex specific death rates for the general population 14.3 deaths would be expected for the same average period. By life table analysis, survival was 98.7% at five years compared to a general population expected 5 year survival of 85.9%. There were no strokes at 5 years of follow-up. (Age and sex specific stroke-free survival for Rochester, MN 1970-1974 is 98% at 5 years). TIA-free survival was 99% at one year (n = 87) and 96% at five years (n = 46). It is concluded that the presence of boundary layer separation in the carotid bulb not only indicates absent or minimal atherosclerotic disease, but is predictive of a favourable long-term outcome with respect to mortality and neurological events.

Age Factors↗
PubMed1992

PCR regimen for enhanced specificity and yield of targeted genomic DNA sequences: ras and p53.

By weighting the PCR reaction in favor of specificity for the target sequence in the beginning cycles and for continued efficient amplification of the sequence into later cycles, we were able to show an improvement in the specificity and quantity of amplified ras and p53 sequences. Increased purity and yield of specific products favorably enhanced post-PCR evaluation and interpretation of results using direct sequencing and single-stranded conformation polymorphism (SSCP) analysis when point mutations were present in DNA from tumor cell lines and tissues.

Base Sequence↗
PubMed1992

Bioactive and immunoreactive FSH and immunoreactive inhibin concentrations in the ovine fetus.

The bioactive (B) and immunoreactive (I) pituitary contents/concentrations of FSH, together with the plasma concentrations of B-FSH, I-FSH and I-inhibin were determined in ovine fetuses at days 55, 75, 90 and 135 of gestation (day 145 = term). The pituitary contents and concentrations of B-FSH and I-FSH increased in both sexes with gestational age. The female fetuses had significantly (P < 0.01) higher pituitary contents/concentrations of B-FSH and I-FSH than the male fetuses at days 75 and 135. The pituitary B/I ratios of FSH were not significantly different with age or sex. The plasma concentrations of B-FSH remained relatively constant from days 75 to 135, with no significant differences between sexes or with age. In contrast, the plasma concentrations of I-FSH reached a peak at day 90 and then declined towards term in both sexes. At all gestational ages except day 55, the female fetuses had significantly (P < 0.05) higher plasma concentrations of I-FSH than the males. In both sexes, the plasma B/I ratios of FSH were lowest at day 90 and had increased again by day 135, with the male fetuses having significantly (P < 0.05) higher B/I ratios compared with the female group at days 75 and 135 but not at day 90. At all gestational ages, the plasma concentrations of I-inhibin declined throughout gestation in the female fetuses, whereas in the males they reached a nadir at day 75 and then increased towards term. The concentrations of I-inhibin were significantly (P < 0.01) higher in the male fetuses compared with the females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

A triangulation method for the quantitative measurement of arterial blood velocity magnitude and direction in humans.

A triangulation method has been applied to a duplex ultrasound scanner to quantify blood flow velocities in two dimensions. A position locating system (PLS) connected to the scanhead locates the sample volume (SV) in 3-D space to a precision of 1 mm. The PLS is used to obtain flow velocity data from two independent lines of sight in the human femoral artery. Data are gathered from anatomic sites of interest along one line of sight. Later the computer directs the SV to interrogate the same points in space from a second line of sight. Water tank studies using both constant velocity and pulsatile string targets were used to validate the method. Velocity magnitudes could be calculated to within 5% error for Doppler angles below 75 degrees for various string depths and speeds; the error in Doppler angle calculation was usually less than 3 degrees. Results from the superficial femoral artery show flow velocity vectors are nearly parallel to the vessel walls. Peak systolic velocity magnitudes range from 63-66 cm/s in three presumed normal individuals. Following the validation studies addressed in this paper, this triangulation approach is intended in future work to document the complex nonaxial character of blood flow that occurs normally at branch points and in regions of intraluminal disease.

Blood Flow Velocity↗
PubMed1990

Effects of the synthetic glucocorticoid dexamethasone on reproductive function in the ewe.

Glucocorticoids have been found to inhibit reproductive function in most domestic species studied but, in the ewe, preliminary reports suggest that glucocorticoids may have little or no effect. This study investigated the effects of the synthetic glucocorticoid dexamethasone on oestrus and ovulation rate in ewes during the breeding season and gonadotrophin secretion in the breeding and non-breeding seasons. In cyclic ewes, dexamethasone treatment at rates of up to 2 mg/day did not affect the natural or pregnant mare serum gonadotrophin-stimulated ovulation rate, or the timing and incidence of behavioural oestrus (P greater than 0.05). Dexamethasone administration (2 mg/day) had no effect on LH secretion or the plasma LH response to a 1 micrograms injection of gonadotrophin-releasing hormone (GnRH) in ovariectomized ewes in the breeding and non-breeding seasons, and did not compromise the inhibition of plasma LH levels during chronic treatment with oestrogen. Similarly, dexamethasone had no effect on plasma FSH concentrations, but significantly (P less than 0.05) reduced the plasma FSH response to a 1 micrograms GnRH injection during chronic negative treatment with oestrogen in ovariectomized ewes. Collectively, these data show that in these experiments dexamethasone did not significantly modify reproductive function in the ewe, a finding that is in contrast to that found in other domestic species.

Animals↗
PubMed1990

Effects of modifying gonadotrophin-releasing hormone input before and after the oestrogen-induced LH surge in ovariectomized ewes with hypothalamo-pituitary disconnection.

The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 micrograms oestradiol benzoate (OB). The ewes were given a bolus pulse of 2.25 micrograms GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P less than 0.05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P less than 0.05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. In experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 micrograms/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P less than 0.05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen.

Animals↗
PubMed1990

Testing ultrasonic pulsed Doppler instruments with a physiologic string phantom.

The spatial, temporal, and frequency resolution of conventional ultrasonic Doppler instruments and the time/space distortions in two-dimensional color Doppler imaging systems can be measured using a pulsatile moving string target. The diameter of the string is small compared with the Doppler sample volume, the velocity (speed and direction), acceleration and timing of the string motions are precisely known with reference to the R wave timing mark, and the spatial location of the string is known. A loop of surgical thread or monofilament fishline running between pulleys is driven by a motor that provides constant string speeds from 0.05 to 150 cm/s and variable string speeds programmed to mimic arterial velocity waveforms from the carotid, aortic, and femoral arteries. Constant string speeds are used to evaluate the Doppler sensitivity, frequency processing, and sample volume size; pulsatile movement of the string provides a physiologic model to evaluate the temporal performance of conventional Doppler systems and the temporal and spatial performance of two-dimensional color Doppler imaging scanners.

Blood Flow Velocity↗
PubMed1990

Recent advances in carotid artery evaluation.

This chapter was intended to provide an overview of ultrasound duplex scanning at the human carotid bifurcation. Although results of clinical studies are useful in patient management, much remains to be learned in the area of understanding the disease process and determining what features, obtainable by ultrasound, will predict clinical outcome. Listed below are the important points covered by this chapter. 1. Ultrasound duplex scanning can detect and quantify carotid artery disease with respect to the gold standard of contrast arteriography. 2. Contrast arteriography is not the ideal gold standard for assessment of cartotid artery disease. A new standard incorporating attributes of not only anatomy but also physiology is needed. 3. Using currently available ultrasound systems it is not possible to obtain the Doppler angle (i.e., the angle formed by the transducer axis and the blood flow-velocity vector). This angle is often estimated by the angle formed by the transducer axis and the axis of the blood vessel. This assumes that the flow-velocity vectors are axial, which turns out to be a poor assumption at bifurcations, curves, and sites of intraluminal disease. Specifying the Doppler angle involves assumptions that should always be kept in mind. 4. All Doppler data should be collected at the same angle formed by the sound beam relative to the vessel axis. Whereas results of Doppler studies can be reported in units of either frequency or velocity, assumptions made about the Doppler angle and acquiring data at arbitrary angles can produce large errors when quantifying flow velocities. 5. Blood flow disturbances cannot automatically be equated with the presence of disease. Some disturbances are localized secondary blood flow patterns produced by changes in vascular geometry coupled with pulsatile flow. 6. The lack of blood flow disturbances cannot automatically be equated with a normal or disease-free artery. Accumulation of plaque within the sinus region at the minimal and moderate disease stages appears to eliminate or attenuate local flow disturbances characteristic of a normal bifurcation. 7. An understanding of the blood flow patterns at clinical sites of interest is important to the correct interpretation of data. Both the imaging and pulsed Doppler modalities are essential to this understanding: the imaging capability to place the pulsed Doppler sample volume and appreciate changes in vascular anatomy, and the pulsed Doppler to obtain the character of blood flow at specific sites within the blood vessels.

Carotid Arteries↗
PubMed1989

Specificity and association constants of 33 monoclonal antibodies to human IgA epitopes.

We used an immunofluorescent sequential-saturation-of-antibody assay and an interactive computer program for Scatchard analysis to determine association constants (Ka) of 33 murine monoclonal antibodies (Mabs) specific for human IgA epitopes. Ka ranged from 0.37 to 690 x 10(7) liters per mole (an approximate 1900-fold difference). Specificity was validated with a panel of 18 highly purified IgA1 and IgA2 myeloma proteins and secretory IgA using an immunofluorometric assay. Western blots of bacterial IgA protease digests were used to locate the epitopes of IgA specific Mabs in either the Fab, Fc, or hinge region. Mabs specific for unique epitopes on secretory IgA or free secretory component (FSC) were produced and evaluated.

Animals↗
PubMed1989

Should results of ultrasound Doppler studies be reported in units of frequency or velocity?

There is a current tendency to report the results of ultrasound Doppler studies in units of velocity instead of Doppler frequency. This is probably motivated by the intuitive feeling that blood flow studies should naturally be reported in cm/s and the notion that "velocity" is a normalizing factor for Doppler ultrasound studies. In order to determine velocity, the Doppler angle theta or angle formed by the ultrasound beam and flow velocity vector, must be known. It is not possible, using currently available systems, to obtain an accurate estimate of this angle. The physics related to the Doppler equation are reviewed in this paper along with examples to illustrate the origin and magnitude of errors that could arise when reporting in units of velocity. Guidelines are provided for thinking about and reporting results of Doppler studies in units of velocity. An understanding of the Doppler equation and its use in clinical studies are promoted in this paper to enhance the diagnostic usefulness of Doppler ultrasound studies and to reduce serious errors which could lead to faulty information dictating patient management.

Blood Flow Velocity↗
PubMed1989

An ultrasonic measurement of superficial femoral artery wall thickness.

An ultrasonic measurement of the superficial femoral artery wall thickness was performed on 16 volunteers. The measurement included all echogenic tissue between the lumen of the superficial femoral artery and the lumen of the superficial femoral vein. The average arterial wall plus vein wall thickness in volunteers with peripheral arterial disease was 2.13 +/- 0.87 mm, significantly greater than the 1.27 +/- 0.50 mm found in those without detectable peripheral arterial disease.

Aged↗
PubMed1989

Recommended guide to the evaluation of permanent impairment of the temporomandibular joint.

This paper provides a method to evaluate the extent of permanent injury to the temporomandibular joint. The authors, working as the Committee on Permanent Impairment for the American Academy of Head, Facial, Neck Pain and TMJ Orthopedics, have used the same values as the American Medical Association has used in their Guides to the Evaluation of Permanent Impairment for other disk-protected and functional joints. These Guides may then serve as a tool to help physicians and dentists who treat temporomandibular joint injuries to rate the degree of permanent injury. These Guides may be combined with other areas of impairment that are already described and valued in the Guides to the Evaluation of Permanent Impairment published by the AMA. These Guides provide a range and each injury should be evaluated on an individual basis. We urge you to use these Guides conservatively and in harmony with good clinical judgement.

Disability Evaluation↗
PubMed1989

Diagnostic significance of flow separation in the carotid bulb.

Pulsatile blood flow within the normal carotid sinus involves at least two distinct components. That near the flow divider is laminar and antegrade, whereas a boundary layer separation zone in the posterolateral aspect exhibits transient blood flow reversal. It is now possible to document these flow velocity components using pulsed Doppler ultrasound methods. When atherosclerosis develops, it preferentially involves the posterolateral bulb region, obliterating the normal configuration of the sinus with consequent loss of the flow separation zone. It was therefore hypothesized that if flow separation could be detected, it should be predictive of a normal angiogram. To assess this, we evaluated 20 symptomatic patients and two with only bruits found by duplex scanning to have flow separation in either one or both carotid bulbs and who also underwent cerebral angiography. Initial diagnoses were stroke in seven, reversible ischemic neurologic deficit in one, transient ischemic attack in 12, and bruit in two. Flow separation was bilateral in 13 patients (59%). There were 15 patients with symptoms in the territory of a carotid bulb exhibiting flow separation. By angiography, of the 35 bulbs with boundary layer separation, 27 (77%) were normal, with the remainder showing lesions that reduced the diameter of the vessel by 20% or less. Final diagnoses of the 15 patients with symptoms ipsilateral to a carotid sinus exhibiting flow separation were fibromuscular disease in two, lacunar stroke in three, dissection in two, subclavian steal in one, cardiogenic embolus in three, migraine in one, hyperventilation syndrome in one, kink of the mid-internal carotid artery in one, and no diagnosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Arteries↗
PubMed1989

The oestrogen-induced surge of LH requires a 'signal' pattern of gonadotrophin-releasing hormone input to the pituitary gland in the ewe.

Two experiments were conducted with ovariectomized and hypothalamo-pituitary disconnected (HPD) ewes to ascertain the pattern of inputs, to the pituitary gland, of gonadotrophin-releasing hormone (GnRH) necessary for the full expression of an oestrogen-induced LH surge. The standard GnRH replacement to these sheep was to give pulses of 250 ng (i.v.) every 2h; at the onset of experimentation, pulses were given hourly. In experiment 1, groups of sheep (n = 7) were given an i.m. injection of 50 micrograms oestradiol benzoate, and after 10 h the GnRH pulse frequency or pulse amplitude was doubled. Monitoring of plasma LH concentrations showed that a doubling of pulse frequency produced a marked increase in baseline values, whereas a doubling of amplitude had little effect on the LH response. In a second experiment, ovariectomized HPD sheep that had received hourly pulses of GnRH for 16 h after an i.m. injection of oil or 50 micrograms oestradiol benzoate were given either a 'bolus' (2.25 micrograms GnRH) or a 'volley' (500 ng GnRH pulses 10 min apart for 30 min, plus a 500 ng pulse 15 min later). Both groups then received GnRH pulses (250 ng) every 30 min for the next 13 h. Oestrogen enhanced the LH responses to the GnRH treatments, and the amount of LH released was similar in ovariectomized HPD ewes given oestrogen plus bolus or volley GnRH treatments and ovariectomized hypothalamo-pituitary intact ewes given oestrogen. These results suggest that the oestrogen-induced LH surge is initiated by a 'signal' pattern of GnRH secretion from the hypothalamus.

Animals↗
PubMed1988

Estimation of association constants of 42 monoclonal antibodies to human IgG epitopes using a fluorescent sequential-saturation assay.

We measured the association constant (Ka) for 42 murine monoclonal antibodies (MAbs) to human IgG epitopes. Included are antibodies, previously evaluated in an IUIS/WHO collaborative study, to various epitopes on the four subclasses of human IgG - IgG Fc, IgG Fab, kappa, and lambda - and to selected IgG allotopes. We used a sequential-saturation immunofluorescent assay and interactive computer program to determine the Ka by Scatchard analysis. Kas ranged from unmeasurably low by this method (approximately 10(6) L/M) to 3.8 X 10(9) L/M. Some class specific MAbs had large Ka differences for different subclasses and some subclass specific MAbs had large Ka differences for molecules of the same subclass but of different light-chain types.

Antibodies, Monoclonal↗
PubMed1987

Variability in measurement of specific parameters for carotid duplex examination.

The variability of four carotid artery frequency parameters used for classifying disease with duplex scanning was prospectively studied. Forty-eight patients (94 patent carotid arteries) were each examined by two technologists. Measured parameters were the peak systolic frequency (PSF) and the first zero slope from the common carotid artery, and the PSF and end diastolic frequency (EDF) from the internal carotid artery. Measurements from all the examinations were made twice by each technologist. Interobserver, intraobserver, and interpatient variability in measurement of the first zero slope was so great that we have abandoned its use. Measurement of variability for PSF and EDF was much less (correlation coefficients 0.68 to 0.92). These parameters were measured with sufficient precision to warrant their continued use for important decision steps in classifying carotid artery disease. Interpatient differences in PSF sufficient to cause disagreement regarding the hemodynamic significance of carotid disease occurred in only three instances. In each of these cases the differences were due to examination technique (failure to identify a very distal internal carotid artery stenosis, difficulty distinguishing between a kink and a stenosis, and failure to recognize an improper Doppler angle). We conclude that the variability of PSF and EDF is within clinically acceptable levels and is mainly due to examination technique rather than measurement of waveform parameters or changes in patient hemodynamics.

Arterial Occlusive Diseases↗