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Biomedical subjects

D Davidson

Publications and source records attributed to D Davidson.

At least 199 records · Page 11Linked to original sources
PubMed1990

Ultrasound of the normal nongravid uterus: correlation with gross and histopathology.

Accurate assessment of uterine size and significance of uterine enlargement are common clinical problems. We examined 156 patients by sonography prior to scheduled hysterectomy. Uterine volumes from normal-sized uteri were calculated from the sonograms using the equation of a prolate ellipsoid formula, and these calculated volumes were highly correlated with actual measured uterine volumes. Mean values and normal ranges of uterine weight were determined. These values are of particular value in postmenopausal patients in whom subjective evaluation of uterine enlargement is often difficult. When a sonographically enlarged, but otherwise normal uterus is discovered, it may contain a leiomyoma or other pathology not morphologically detectable by ultrasound.

Age Factors↗
PubMed1990

Fine-needle aspiration biopsy: an analysis of 89 head and neck cases.

In a recent 2-year period, 89 fine-needle aspiration biopsies (FNAB) were performed on head and neck lesions in 81 patients from 6 to 97 years of age. Eighty-four of the FNABs were considered diagnostic. Thirty of the aspirates were diagnosed as benign whereas 54 were diagnosed as malignant. Three specimens were suspicious for malignancy, and 2 specimens were considered nondiagnostic. The most common malignant diagnosis was squamous cell carcinoma, which involved 32 of the specimens. The most common benign diagnosis was pleomorphic adenoma. Subsequent surgical biopsy specimens were available in 45 of the patients. Of these, 41 were consistent with the FNAB diagnosis, whereas 4 were not.

Adenocarcinoma↗
PubMed1990

Role of leukotriene C4 in pulmonary hypertension: platelet-activating factor vs. hypoxia.

The aim of this study was to determine whether leukotriene C4 (LTC4) is a mediator of hypoxic pulmonary vasoconstriction. We hypothesized that similar increases in LTC4, detected in the lung parenchyma and pulmonary vascular compartment during cyclooxygenase blockade with indomethacin (INDO), would be observed during an equal increase in pulmonary arterial pressure caused by acute alveolar hypoxia (HYP, 100% N2) or platelet-activating factor (PAF, 10 micrograms into the pulmonary artery). Rat lungs were perfused at constant flow in vitro with an albumin-Krebs-Henseleit solution. Mean pulmonary arterial pressure (n = 6 per group) increased from a base line of 10.9 +/- 1.2 to 15.8 +/- 2.1 (HYP + INDO) and 15.5 +/- 1.9 (SE) Torr (PAF + INDO). LTC4 levels increased only in response to PAF + INDO; perfusate levels increased from 0.4 +/- 0.07 to 5.3 +/- 1.1 ng/40 ml, and lung parenchymal levels increased from 1.9 +/- 0.07 to 22.8 +/- 5.3 ng/lung. Diethylcarbamazine (lipoxygenase inhibitor) reduced PAF-induced lung parenchymal levels of LTC4 by 68% and pulmonary hypertension by 63%. We conclude that 1) LTC4 is not a mediator of hypoxic pulmonary vasoconstriction and 2) intravascular PAF is a potent stimulus for LTC4 production in the lung parenchyma.

Animals↗
PubMed1990

Endothelium-derived relaxing factor: presence in pulmonary and systemic arteries of the newborn guinea pig.

Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, is a potent vasodilator produced by some arteries in response to acetylcholine (ACh) and bradykinin (BK). ACh and BK are potent dilators of perinatal pulmonary and systemic arteries. The objectives of this study were to determine if EDRF is present in newborn vessels and if EDRF mediates the vasodilator actions of ACh and BK. Arterial rings from newborn guinea pigs, 1 to 3 d old, were obtained from a branch of the main pulmonary artery and the descending aorta for isometric force bioassays. At their optimal resting tension, the rings were preconstricted with phenylephrine 10(-5) M in Krebs-Henseleit solution before adding incremental doses of ACh or BK. If the endothelium was intact, ACh (10(-5) M) relaxed pulmonary arteries and aortas (64 +/- 7%, 72 +/- 9% relaxation, respectively, mean +/- SE). ACh-induced relaxation (ACh 10(-5) M) in the pulmonary artery and aorta, respectively, was significantly (p less than 0.05) attenuated by 1) endothelial removal (11 +/- 9%, 28 +/- 10%) by rubbing the ring lumen; 2) methylene blue, 10(-6) M, (6 +/- 8%, 7 +/- 3%) that inhibits EDRF-associated cGMP production in smooth muscle; and 3) methemoglobin, 10(-5) M, (13 +/- 9%, 17 +/- 7%) that binds EDRF. The results for BK were similar to ACh for the pulmonary artery but BK did not relax the aorta. Indomethacin diminished relaxation of the pulmonary artery and aorta to the submaximal dose (10(-5) M) of ACh but indomethacin did not effect the relaxation to ACh 10(-4) M or BK. We conclude that EDRF is produced in the guinea pig pulmonary artery and descending aorta at birth and that EDRF is a mediator of the vasodilator actions of ACh and BK. Vasodilation by ACh may also involve activation of the cyclooxygenase pathway.

Acetylcholine↗
PubMed1988

131I-metaiodobenzylguanidine uptake in the isolated rat lung: a potential marker of endothelial cell function.

The pulmonary vascular endothelial cell plays an important role in the uptake of circulating biogenic amines. In cultured adrenomedullary cells, metaiodobenzylguanidine (MIBG) and norepinephrine (NE) are taken up by the same sodium-dependent active transport system. To examine whether a similar process occurs in the lung, the mechanism of single pass 131I-MIBG accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. MIBG lung accumulation was measured as the percent extraction per g of lung tissue. In control experiments the extraction was 19.7 +/- 2.3%/g (n = 38) using a perfusate containing 0.01 microM MIBG. MIBG accumulation was significantly depressed (% decrease from control) by: cold media at 4 degrees C (84%), 0.5 mM ouabain (67%), 10 microM imipramine (70%), 0.7 microM serotonin (22%) and 40 mM K+ (48%). Pulmonary uptake of MIBG was characterized by Michaelis-Menten kinetics (Km = 0.92 x 10(-6) M and Vmax = 2.09 x 10(-9) moles/g per min). The addition of NE (0.5 microM) also altered MIBG uptake such that the Km and Vmax became 0.52 x 10(-6) M and 0.93 x 10(-9) moles/g per min, respectively. The results indicate that MIBG accumulation in the lung involves sodium-dependent, energy-requiring, active transport mechanisms similar to those known to exist for norepinephrine, and suggest that MIBG may be useful as a marker of pulmonary endothelial cell function.

3-Iodobenzylguanidine↗
PubMed1988

Pulmonary hemodynamics at birth: effect of acute cyclooxygenase inhibition in lambs.

The effect of acute cyclooxygenase (CYO) inhibition on the cardiopulmonary adjustments at birth was examined in chronically instrumented, unanesthetized, term lambs before, during, and after cesarean section (spontaneous respiration). One of three infusions was started 20 min before birth: saline control (C, n = 6), indomethacin (I, n = 6), or meclofenamate (M, n = 3). The stable metabolite of prostacyclin, plasma 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, aorta), was measured by radioimmunoassay as an index of CYO activity. Indomethacin blocked the rise of 6-keto-PGF1 alpha observed in control lambs after birth and indomethacin-treated lambs exhibited an attenuation of the postnatal decrease in mean pulmonary arterial pressure. Pulmonary arterial pressure (Ppa) was 53 +/- 2 and 47 +/- 2 Torr (mean +/- SE) at 15 min and 40 +/- 3 and 34 +/- 2 Torr at 120 min in I and C groups, respectively. There were no serial or group differences in cardiac output and cardiac right to left shunt (indicator dilution) from 15 to 120 min after birth. Arterial PO2 (PaO2) was not different between groups: 37 +/- 4 Torr at 15 min and 47 +/- 5 min at 120 min after birth (control lambs). The results for I and M were similar for all measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

A gene with sequence similarity to Drosophila engrailed is expressed during the development of the neural tube and vertebrae in the mouse.

The mouse genes En-1 and En-2 display sequence similarity, in and around the homeobox region, to the engrailed family in Drosophila. This paper describes their pattern of expression in the 12.5-day mouse embryo as determined by in situ hybridization. En-2 is expressed in a subset of cells expressing En-1. Both genes are expressed in the developing midbrain and its junction with the hindbrain. In addition, En-1 is expressed in the floor of the hindbrain, a restricted ventrolateral segment of the neural tube throughout the trunk and anterior part of the tail, the dermatome of tail somites, the centrum and costal processes in developing vertebrae, a restricted region of facial mesenchyme and the limb-bud ectoderm. Supplementary studies of 9.5-day and 10.5-day embryos showed that the same pattern of expression pertained in the neural tube, but that expression in the somites is at first confined to the dermatome and later found at a low level in restricted sclerotomal regions. Both genes are expressed in restricted domains which do not cross tissue-type boundaries. In several instances, however, boundaries of expression lie within morphologically undifferentiated tissue. These results suggest that En-1 and En-2 may be involved in the establishment or maintenance of the spatial integrity of specific domains within developing tissues.

Animals↗
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↗