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D Davidson

Publications and source records attributed to D Davidson.

At least 217 records · Page 12Linked to original sources
PubMed1988

A new regimen of interleukin 2 and lymphokine-activated killer cells. Efficacy without significant toxicity.

Adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer (LAK) cells has proved to be successful in the treatment of some patients with metastatic cancer, but not without a significant degree of associated toxic effects. The primary goal of this study was to substantially reduce the toxicity of this complex and expensive treatment, while maintaining or improving efficacy. To this end, 29 patients were treated with LAK cells in conjunction with a low-dose regimen of interleukin 2 and a prolonged period of administration following LAK cell infusion. This protocol resulted in a considerable reduction in toxicity, as compared with that described in previous studies, without compromising the efficacy. This study offers further confirmation that adoptive immunotherapy of metastatic cancer can be clinically beneficial to patients for whom no other effective therapy is presently available.

Adult↗
PubMed1987

Overproduction of polyomavirus middle T antigen in mammalian cells through the use of an adenovirus vector.

To overproduce biologically active polyomavirus middle T antigen, we used an adenovirus vector and human 293 cells as hosts. Two helper-independent recombinant adenoviruses were isolated that contain a hybrid transcription unit, in differing orientations, at a site in the adenovirus genome from which the E1a and most of the E1b transcription units have been deleted. The hybrid transcription unit consists of the adenovirus type 2 major late promoter and tripartite leader and a cDNA segment capable of encoding polyomavirus middle T antigen and accompanying 3' RNA-processing signals. Both recombinant viruses were stable and replicated to high titers in human 293 cells. The polyomavirus sequences were expressed, predominantly at late times after infection of 293 cells, to yield mRNAs that encoded middle T antigen. One of the recombinant viruses also expressed a middle T antigen-related protein in 293 cells. The latter was translated from one of several novel mRNA species that resulted from aberrant splicing and incomplete RNA processing of precursor RNA transcripts. Comparison of the amount of middle T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with either of the recombinant adenoviruses, under optimal conditions for each system, revealed at least a 10-fold greater yield of the protein on a per-cell basis in the latter system than in the former. The recombinant-virus-encoded middle T antigen was biologically active, as evidenced by its ability to associate with and serve as a substrate for human pp60c-src. The functionality of the middle T antigen was further confirmed by demonstrating that both recombinant viruses efficiently transformed Rat-1 cells. These recombinant viruses will be useful to overproduce middle T antigen and to introduce the polyomavirus oncogene into a wide variety of mammalian cells.

Adenoviruses, Human↗
PubMed1987

Circulating vasoactive substances and hemodynamic adjustments at birth in lambs.

Circulating vasoactive substances and hemodynamics were examined in chronically instrumented unanesthetized lambs before, during, and after cesarean section (spontaneous respiration). One of three infusions were started 20 min before birth: saline control (n = 10), saralasin (n = 5), or captopril (n = 6). Control lambs exhibited peak (means +/- SE) increases above fetal base line at 5 min after birth in plasma renin activity (5.0 +/- 1.1 to 11.0 +/- 3.4 ng.ml-1.h-1), angiotensin II (ANG II, 37 +/- 6 to 141 +/- 45 pg/ml) and total catecholamines (318 +/- 35 to 3,821 +/- 580 pg/ml). Mean systemic arterial pressure (Psa) and arterial O2 partial pressure (PaO2) increased more rapidly and to a greater extent by 1 h after birth in control lambs (Psa, 65 +/- 1 Torr; PaO2, 45 +/- 3 Torr) compared with the captopril group (Psa, 53 +/- 2 Torr; PaO2, 31 +/- 4 Torr) and the saralasin group (Psa, 56 +/- 2 Torr; PaO2, 27 +/- 3 Torr). Intravenous infusions of ANG II in control lambs, 2 h after birth resulted in a preferential systemic vs. pulmonary pressor response. The results demonstrate that at birth ANG II formation fosters the postnatal rise in Psa and PaO2, and high levels of circulating catecholamines may support postnatal cardiac output and Psa.

Adaptation, Physiological↗
PubMed1987

Timekeeping by frog embryos, in normal development and after heat shock.

(1) Timekeeping refers to the uniformity of development in time. The precision of timekeeping is measured by the extent to which embryos, within an initially synchronous population, come to diverge in the course of their development. (2) Divergence is measured as the variation in the stage of development reached between embryos allowed to develop for a fixed period of time. The lower the variation the better the timekeeping. (3) Divergence among frog embryos that started development at the same time is hardly measurable after approx. 100 h of development. This striking uniformity indicates good timekeeping. (4) Timekeeping is not impaired among the survivors following heat shocks that retard development and disturb and curtail morphogenesis. (5) The immediate effect of heat shock is a stoppage of development, the duration of which is the same for all embryos in the same treatment batch. The embryos react to heat shock by rescheduling their development with the interpolation of a rest, the duration of which is controlled to the same precision as normal development. The postponement of development, without impairment of timekeeping, implies dis-engagement of the processes of morphogenesis from, and their subsequent re-engagement with, an enduring rate-determining activity unaffected by heat shock. (6) We have searched for embryos whose rate of development was disturbed by heat shock to run slower or faster than the norm. We have found none. It seems that the (temperature-compensated) rate of development is invariant up to the moment of failure, or a change is immediately lethal.

Animals↗
PubMed1986

An inexpensive microcomputer digital imaging system for densitometry: quantitative autoradiography of insulin receptors with 125I and LKB Ultrofilm.

This article describes a video digitizing system designed for measuring film optical density. The system, which is based on a 6-bit (64 gray level) digitizer, solid state video camera, and Apple II microcomputer, digitizes a rectangular area selected by the operator and converts the gray level values into preselected standard units. In order to develop autoradiographic standard curves for quantitative autoradiography with 125I-insulin, liver slices labeled with 125I-insulin and plastic sections containing known amounts of tritium were apposed to the same sheet of LKB Ultrofilm for exposures of 1-7 days. The results indicate that 3H plastic standards can be used to calibrate QAR of 125I-labeled ligands with LKB Ultrofilm. The Apple system was also used to measure binding of 125I-insulin to the external plexiform layer (EPL) in slices of the rat olfactory bulb. Results suggest that the EPL has two binding sites for insulin, a high affinity site with Kd = 1.0 X 10(-8) M and a low affinity site having a Kd = 1.4 X 10(-5) M.

Animals↗
PubMed1986

Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia.

Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments.

Acid-Base Equilibrium↗
PubMed1986

Hormones, mood and sexuality in lactating women.

Of 25 primiparous women, investigated prospectively for six months post-partum, 19 persisted with breast feeding and six changed to artificial during the first six weeks. Sexual activity, mood, and feeding patterns were recorded in weekly diaries. Hormones were measured from weekly urine samples (oestrogen and pregnanediol) and fortnightly blood samples (prolactin, testosterone, androstenedione, and sex hormone binding globulin). In breast-feeding women, testosterone and androstenedione levels were significantly lower in those who reported severe reduction in sexual interest. Changes in sexuality or mood were not related to levels of prolactin or oestrogen, or to the return of follicular activity, which was delayed in persistent breast feeders. The relationships of mood, sexuality, and hormones are discussed.

Adult↗
PubMed1985

Do pregnancy complications contribute to neurodevelopmental disability?

In the Dundee Development Screening Programme all children born in Dundee in 1974 and 1975 were screened at intervals during infancy and childhood. The obstetric and neonatal antecedent factors in 300 of the 322 singleton children with neurodevelopmental disability (index group) were compared with those of the 600 children of normal development born immediately before and after each child with disability (control group). Low social class was associated with mental retardation, global delay, speech delay, and behavioural disorder, but not with cerebral palsy or motor delay. With the exception of cerebral palsy, strong associations were found between all categories of disability and severe hypertension, unclassified antepartum haemorrhage, and preterm uterine activity. Cerebral palsy was not associated with antepartum complications, but was with fetal tachycardia during labour. Our data suggest that neurodevelopmental disability may, in many cases, originate during pregnancy and delivery.

Birth Weight↗
PubMed1984

Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.

The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (PaO2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, PaCO2, PaO2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most of the gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different hemodynamic patterns between control and saralasin groups emerged upon reoxygenation, including an elevation from base line in blood pressure and systemic vascular resistance in the control group. Cardiac work (heart-rate systolic pressure product) in the control group remained elevated upon reoxygenation while coronary blood flow returned to base-line values. Saralasin reduced cardiac work upon reoxygenation and restored the match between coronary blood flow and work. We conclude that plasma renin activity and oxygen tension together govern angiotensin II levels for an optimal level of systemic vasomotor tone during hypoxia. However, upon reoxygenation, bolus production of angiotensin II may result in pathophysiologic circulatory patterns, such as impairment in oxygen delivery to the myocardium proportional to persistently elevated cardiac work in the immediate postresuscitation period.

Angiotensin II↗
PubMed1984

Dermal cells form strong adhesions to the basement membrane during the development of feather primordia in chick skin.

Experiments are described which provide a direct measure of the adhesion between dermis and epidermis during the development of feather primordia in chick dorsal skin in culture. The epidermis was peeled from the dermis and the surfaces so exposed were examined under the scanning electron microscope: regions of strong adhesion between the tissues were revealed as areas where their separation was incomplete. The results show that soon after primorida become morphologically distinct, cells from the surface of dermal condensations form adhesions to the basement membrane which are stronger than those between dermis and epidermis interplumar skin. These adhesions may help to hold the epidermis and dermis together during the outgrowth of the primordium.

Animals↗