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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

Use of exoglycosidases from Mercenaria mercenaria (hard shelled clam) as a tool for structural studies of glycosphingolipids and glycoproteins.

The hepatopancreatic extract of M. mercenaria (hard shelled clam) was found to be a rich source for at least 16 different glycosidases. These glycosidases were successfully employed for the degradation of oligosaccharides, glycolipids, and glycoproteins at analytical as well as preparative levels. The identified glycosidases differ considerably in their stability profiles with respect to time and temperature of storage and presence of glycerol. However, most of the enzymes show higher activity at pH 4.5 than at pH 7.0, and could be bound on a DEAE CL-6B Sepharose anion-exchange column suggesting similar charge characteristics on the protein surface. A Gal beta 1, 3R linkage-specific beta-galactosidase activity has also been detected in the glycosidase-enriched fraction and has been utilized to obtain quantitative conversion of the ganglioside GM1 to GM2 on a preparative scale. The glycosidase-rich extract does not have detectable protease activity at the pH of optimal glycosidase activity (pH 4.5) and, hence, can be safely used for specific hydrolysis of carbohydrate moieties of glycoproteins and glycopeptides. This is the first report to characterize a repertoire of glycosidases from an inexpensive, dependable and convenient source that can be easily employed for compositional studies involving glycoconjugates.

Animals↗

Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change.

The neuroendocrine response to L-tryptophan infusion was measured at two stages of the menstrual cycle, premenstrually and postmenstrually, in 13 women with and 13 women without premenstrual depression (the MC and NMC groups respectively). Previous studies have shown that in non-depressed women, this challenge test results in an increase in circulating prolactin and growth hormone. In depressed women both responses are blunted. In this study the growth hormone and cortisol responses were smaller in the MC group than the NMC group on both occasions. The prolactin response was blunted premenstrually compared with postmenstrually in both groups. These findings suggest that women who experience premenstrual depression may have neuroendocrine abnormalities throughout the cycle. The neurotransmitter abnormalities reflected in these altered endocrine responses appear to interact with neuroendocrine changes that normally occur premenstrually resulting in a vulnerability to depression at that phase of the cycle.

Adolescent↗

Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated neonatal guinea pig lung.

Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, has been previously identified in the pulmonary and systemic vasculature of the newborn guinea pig using isolated arterial rings. The aim of our study was to determine if EDRF regulates vasomotor tone at the level of resistance vessels in the neonatal pulmonary circulation. Isolated lungs from guinea pigs (1-3 d old, n = 4-8/protocol) were ventilated with room air and perfused with a Krebs-Henseleit solution containing albumin at a constant flow. Angiotensin II (AII, 6 nM) was added to the perfusate to give a stable elevation in mean pulmonary artery pressure (PAP) from 7.0 +/- 1.1 to 19.7 +/- 1.5 torr, a 182 +/- 32% (mean +/- SEM) increase above baseline. Addition of bradykinin (BK, 10 nM) or L-arginine (2 mM) markedly reduced the AII-induced elevation in PAP. At the steady state response to BK (33% above baseline), addition of Hb (10 microM, binds EDRF), NG-monomethyl-L-arginine (NMA, 100 microM, blocks EDRF production), NMA (200 microM), or NMA + Hb, reversed the effect of BK to the following levels of PAP above baseline: 77 +/- 5, 94 +/- 24, 163 +/- 20, or 246 +/- 25%, respectively (p less than 0.05). Indomethacin had no effect on BK-induced vasodilation. In separate studies, NMA (200 microM) increased baseline PAP by 46 +/- 13% and NMA pretreatment raised the AII-pressor response (AII 6 nM) from 133 +/- 49 to 306 +/- 65% above baseline PAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

The lymphocyte-specific tyrosine protein kinase p56lck.

The CD4 and CD8 T cell surface antigens are physically associated with the tyrosine protein kinase p56lck. Accumulating data indicate that p56lck transduces intracellular tyrosine protein phosphorylation signals upon engagement of CD4 and CD8 by major histocompatibility complex (MHC) determinants expressed on antigen-presenting cells (APCs). Recent studies show that these p56lck-related phosphorylation events enhance T cell receptor (TCR)-mediated functions and are critical for the proposed co-receptor roles of CD4 and CD8. p56lck is also capable of enhancing antigen receptor responsiveness in the absence of CD4 or CD8 expression, suggesting that it can directly contribute to the TCR-induced tyrosine phosphorylation signal.

Amino Acid Sequence↗

The candidate Wilms' tumour gene is involved in genitourinary development.

Wilms' tumour is an embryonic kidney tumour thought to arise through aberrant mesenchymal stem cell differentiation and to result from loss of function of a 'tumour suppressor' gene(s). Both sporadic and syndrome-associated Wilms' tumours are accompanied by an increased frequency of abnormalities of the urinary tract and genitalia. Deletional analysis of individuals with the WAGR syndrome (for, Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation) showed that a Wilms' tumour gene lies at chromosomal position 11p13. This led to the isolation of a candidate Wilms' tumour gene, encoding a zinc-finger protein which is likely to be a transcription factor. To gain insight into the role of this candidate gene in normal development and tumorigenesis, we have now performed in situ messenger RNA hybridization on sections of human embryos and Wilms' tumours. The candidate Wilms' tumour gene is expressed specifically in the condensed mesenchyme, renal vesicle and glomerular epithelium of the developing kidney, in the related mesonephric glomeruli and in cells approximating these structures in tumours. The other main sites of expression are the genital ridge, fetal gonad and mesothelium. These data suggest that (1) this candidate is indeed a Wilms' tumour gene, (2) the associated genital abnormalities are pleiotropic effects of mutation in the Wilms' tumour gene itself, in support of recent genetic analysis, and (3) this gene has a specific role in kidney development and a wider role in mesenchymal-epithelial transitions.

Blotting, Northern↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗