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A Tucker

Publications and source records attributed to A Tucker.

At least 73 records · Page 4Linked to original sources
PubMed1994

Calcitonin gene-related peptide modulates pulmonary vascular reactivity in isolated rat lungs.

The role of calcitonin gene-related peptide (CGRP) in modulating hypoxic pulmonary vasoconstriction was assessed. The effects of CGRP and its antagonist [CGRP-(8-37)] on responses to acute hypoxia (3% O2) and angiotensin II (ANG II; 0.4 microgram) were studied in isolated lungs of male Sprague-Dawley rats perfused with a salt solution. Rats with pulmonary hypertension, induced by simulated altitude exposure, were also used to determine the actions of CGRP in a remodeled pulmonary vascular bed. In normotensive (NT) and altitude-exposed (AE) lungs, CGRP injections (10 nM), given after stable pressor responses were attained, attenuated (P < 0.05) subsequent hypoxic pressor responses. Pretreatment with CGRP-(8-37) (10 nM) enhanced (P < or = 0.05) initial ANG II-induced pressor responses in both AE and NT lungs. CGRP-(8-37) pretreatment (10 nM) had little influence on the hypoxic pressor responses in either NT or AE lungs. Results indicate that CGRP modulates hypoxic pulmonary vasoconstriction and that CGRP-(8-37) enhances pressor responses to ANG II in NT and AE rat lungs.

Acclimatization↗
PubMed1994

Influence of carbon dioxide on venous gas emboli production during altitude decompression in goats.

Goats (N = 7) were decompressed from 1,500 m to 9,150, 9,750, or 10,400 m simulated altitude while breathing CO2 tensions of 0, 15, 30, or 46 mm Hg in O2 during 15-min prebreathing and 30-min peak altitude exposures. Risk of decompression sickness was determined by detecting venous gas emboli (VGE) in the pulmonary artery with an implanted Doppler cuff. VGE scores were calculated using the ratio of cardiac cycles containing VGE to total cardiac cycles. The VGE scoring methodology proved sensitive to standard treatment effects (air versus O2 prebreathing). No significant change in VGE scores as a result of varying the inspired CO2 level was detected. Further, no significant change in cardiac index occurred during the various CO2 exposures, and VGE scores were not correlated with cardiac index. Ground-level studies revealed the tension of end-tidal CO2 was significantly elevated at all three levels of inspired CO2, but no change in cardiac index was observed. Short-duration breathing of CO2 in oxygen failed to significantly reduce the risk of decompression sickness as assessed by VGE production.

Altitude↗
PubMed1993

pH-induced structural transitions of bovine serum albumin. Histidine pKa values and unfolding of the N-terminus during the N to F transition.

1. Titration curves have been constructed for all the resolvable resonances of defatted bovine serum albumin [pH meter readings in 2H2O solution (pH*) 2-10], including complete curves for six His residues and partial curves for a further four. Three His residues have unusually low pKa values (less than 5.5). 2. Abrupt discontinuities in the titration curves of nearly all resonances were observed near pH 4.3 (N to F transition), together with a marked loss of chemical shift dispersion at low pH*. No such loss of dispersion occurs in the high pH region previously associated with the N to B transition (approximately pH 8). The NMR data provide strong evidence that the N to F transition is not localised in domain III as had been previously suggested. 3. A localised unfolding of the N-terminal region occurs below pH* 4.5.

Histidine↗
PubMed1993

Detection of aluminium(III) binding to citrate in human blood plasma by proton nuclear magnetic resonance spectroscopy.

Reactions of Al3+ (50-500 mumol l-1) with intact blood plasma and its low relative molecular mass ultrafiltrate (< 5 kDa) have been studied by proton nuclear magnetic resonance spectroscopy. Binding to citrate was detected and was reversed by addition of desferrioxamine. The use of combined exponential and sine-bell functions for the resolution enhancement of spectra of plasma is illustrated.

Aluminum↗
PubMed1993

Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy.

OBJECTIVE: The authors determined whether microscopically positive surgical margins are detrimental to the outcome of early stage breast cancer patients treated with conservation surgery and radiation therapy. SUMMARY BACKGROUND DATA: The optimal extent of breast surgery required for patients treated with conservation surgery and radiation therapy has not been established. To achieve breast preservation with good cosmesis, it is desirable to resect as little normal tissue as possible. However, it is critical that the resection does not leave behind a tumor burden that cannot be adequately managed by moderate doses of radiation. It is not known whether microscopically positive surgical margins are detrimental to patient outcome. METHODS: The records of 259 consecutive women (262 breasts) treated with local excision (complete removal of gross tumor with a margin) and axillary dissection followed by radiation therapy for clinical stage I and II infiltrating ductal breast cancer at Duke University Medical Center and the University of North Carolina between 1983 and 1988 were reviewed. Surgical margins were considered positive if tumor extended to the inked margins; otherwise the margins were considered negative. Margins that could not be determined, either because the original pathology report did not comment on margins, or because the original specimen had not been inked were called indeterminate. RESULTS: Of the 262 tumors, 32 (12%) had positive margins, 132 (50%) had negative margins, and the remaining 98 (38%) had indeterminate margins. There were 11 (4%) local failures; 3/32 (9%) from the positive margin group, 2/132 (1.5%) from the negative margin group, and 6/98 (6%) from the indeterminate group. The actuarial local failure rates at 5 years were 10%, 2%, and 10%, respectively, p = 0.014 positive vs. negative, p = 0.08 positive vs. indeterminate (log rank test). Margin status had no impact on survival or freedom from distant metastasis; 63 patients who originally had positive or indeterminate margins were re-excised. Two of 7 with positive margins after re-excision versus 1/56 rendered margin negative had a local recurrence. CONCLUSIONS: The authors recommend re-excision for patients with positive margins because of improved local control of those rendered margin negative and identification of those patients at high risk for local failure (those who remain positive after re-excision). Because margin status impacts on local control, tumor margins after conservation surgery should be accurately determined in all patients.

Adult↗
PubMed1993

Pulmonary and systemic vascular responsiveness to TNF-alpha in conscious rats.

Endotoxin decreases pulmonary vascular reactivity. Because tumor necrosis factor-alpha (TNF-alpha) is a primary mediator of endotoxemia, we tested whether TNF-alpha altered pulmonary vascular reactivity in conscious adult female rats. Osmotic pumps were implanted intraperitoneally, and low-dose TNF-alpha (62 micrograms, TNF62; n = 7), high-dose TNF-alpha (> or = 250 micrograms, TNF250; n = 5), or saline (n = 5) was administered for 2 wk. Pulmonary pressor responses to 14% O2 and angiotensin II (ANG II, 0.0206 micrograms/min for 10 min) were measured without (day 13) or after (day 14) administration of nitro-L-arginine (4.4 mg/kg iv), an inhibitor of endothelium-derived relaxing factor (EDRF). TNF-alpha administration slightly decreased (P < or = 0.08) baseline pulmonary arterial pressure in TNF250 rats and decreased (P < or = 0.05) hypoxia- and ANG II-induced constrictions in TNF62 and TNF250 rats. Whereas nitro-L-arginine potentiated (P < or = 0.05) pressure responses in control rats, it had no effect on hypoxic responses in TNF-alpha-treated rats. Nitro-L-arginine increased (P < or = 0.05) ANG II-induced vasoconstriction in TNF-alpha-treated rats, but the pulmonary arterial pressure response was still lower (P < or = 0.05) in TNF250 than in control and TNF62 rats. These results suggest that chronic TNF-alpha decreases 1) pulmonary vascular reactivity in the intact rat, 2) hypoxic pulmonary vasoconstriction by a mechanism that is independent of EDRF, and 3) ANG II-induced constriction by a mechanism that is partly EDRF dependent.

Angiotensin II↗
PubMed1993

Muscular strength capacity and altitude response.

To determine the relationship between muscular strength and altitude response, two groups of 7 and 8 subjects were selected from 40 healthy male volunteers, as either high-strength (HS) or low-strength (LS) by performance on a battery of strength tests. There was no difference in hypoxic ventilatory response (HVR) between groups at normobaria. The 4 h hypobaric conditions in a Hypo-hyperbaric Chamber (PBar = 429) produced qualitatively similar altitude-induced physiological responses. However, the LS group showed a lower SaO2 at 2 and 4 h of hypoxia (p < 0.05). Furthermore, PETCO2 and PVCO2 were lower and PETO2, PVO2, and pH were greater in the HS group during hypobaria, although these differences did not achieve statistical significance. Muscular strength index (body weight divided by strength test values) was negatively correlated with PvCO2 (r = -0.63, p = 0.0074), PETCO2 (r = -0.62, p = 0.006) and positively with SaO2 (r = 0.54, p = 0.018) at altitude. These findings suggest that the HS group may have become more hypocapnic and alkalotic (suggesting a greater ventilatory response), and consequently less hypoxic than the LS group.

Adult↗
PubMed1992

Uptake of Al3+ into the N-lobe of human serum transferrin.

We have studied the binding of Al3+ to human serum apotransferrin (80 kDa) and recombinant N-lobe human apotransferrin (40 kDa) in 0.1 M-sodium bicarbonate solution at a pH meter reading in 2H2O (pH*) of 8.8 using 1H n.m.r. spectroscopy. The results show that for the intact protein, preferential binding of Al3+ to the N-lobe occurs. Molecular modelling combined with an analysis of ring-current-induced shifts suggest that n.m.r. spectroscopy can be used to probe hinge bending processes which accompany metal uptake in solution.

Aluminum↗
PubMed1992

Proton NMR studies of bovine serum albumin. Assignment of spin systems.

A variety of one- and two-dimensional 1H-NMR methods have been applied to the study of defatted 66.5-kDa bovine serum albumin in solution. 1. The majority of the protons gave rise to broad unresolved resonances and spectral enhancement methods for one-dimensional spectra were investigated in detail. A combination of exponential and sine-bell functions was particularly effective. 2. The presence of contaminating glycoproteins in some commercial samples of bovine serum albumin was readily detectable from their N-acetyl resonances at about 2.1 ppm. 3. The release of bound Cys (from mixed disulphide at Cys34) was observed after addition of dithiothreitol. 4. Through the use of two-dimensional shift-correlated spectroscopy, assignments of some 80 spin systems to amino acid type were made. 5. The pKa of the N-terminal Asp was measured as 7.8 (0.1 M phosphate buffer, 310 K). 6. 1H NMR spectra of bovine, human, porcine and rat serum albumins have been compared. Using sequence comparisons, specific assignments have been made for the N-terminal residues of bovine (Asp-Thr-His), human (Asp-Ala-His), porcine (Asp-Thr-Tyr) and rat (Glu-Ala-His) albumins, and for Thr189, Tyr155 and His59/377 of bovine albumin. 7. These NMR data suggest that certain local regions of bovine serum albumin are highly mobile yet structured in solution, and demonstrate that the application of both one- and and two-dimensional NMR methods will allow more detailed investigations of structural transitions in serum albumins induced by, for example, pH, drug and metal binding.

Amino Acid Sequence↗
PubMed1992

Is transcutaneous electrical nerve stimulation of any value during cervical laser treatment?

OBJECTIVE: To assess the value of transcutaneous electrical nerve stimulation (TENS) during cervical laser therapy. DESIGN: Randomized three arm controlled clinical trial comparing (i) TENS, (ii) local anaesthetic and (iii) TENS plus local anaesthetic (direct infiltration of 2% lignocaine and 0.03 iu/ml octopressin). SETTING: Colposcopy Unit adapted to run randomized trials. SUBJECTS: 100 women with CIN and no previous experience of cervical surgery. MAIN OUTCOME MEASURE: Visual linear analogue pain scores. RESULTS: The median pain score associated with TENS was greater than the score associated with local anaesthesia (23% compared with 17%; P = 0.1). Combining TENS with local anaesthesia did not further reduce pain scores. CONCLUSION: Although there was considerable consumer satisfaction with TENS it provided no additional pain relieving effect in addition to direct infiltration of lignocaine and it is inferior to lignocaine alone. We are unable to advocate the use of TENS for laser treatment of the cervix.

Adult↗
PubMed1992

Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs.

Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025-0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Heart and lung alterations in neonatal rats exposed to CO or high altitude.

We wished to determine whether cardiac changes produced by CO are related to the development of pulmonary hypertension and whether they are specific for CO or also occur with high-altitude exposure. Newborn male Sprague-Dawley rats were exposed to 500 ppm CO for 32 days (CO) at Detroit, MI or to 11,500-ft simulated altitude at Fort Collins, CO (barometric pressure 495 Torr; 11K); ambient air controls were maintained at Detroit (657 ft, 200 m; AIR) and at Fort Collins (5,000 ft, 1,524 m; 5K). Rats were maintained at Fort Collins after 34 days of age. Hematocrit was elevated to a greater extent in the CO than in the 11K group 2 days postexposure; however, no differences existed 40, 76, or 112 days postexposure. Right ventricle (RV) and left ventricle plus septum (LV + S) mass in CO rats were increased 38.0 and 37.4%, respectively, relative to the AIR group 2 days after CO exposure; RV and LV + S in the 11K group were increased 55.7 and 9.3%, respectively, relative to the 5K group. Cardiac hypertrophy declined in the CO and 11K groups postexposure but remained significant for the RV, reaching 20.7% above the AIR group (CO) and 29.7% above the 5K group (11K) at 145 days of age. By use of an in vitro preparation, pulmonary vascular resistance (PVR) and pulmonary arterial pressure were significantly increased immediately after altitude but not after CO exposure and remained elevated in adulthood after altitude exposure. PVR was correlated with hematocrit in altitude- but not in CO-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Factors influencing the idiopathic development of pulmonary hypertension in the fawn hooded rat.

Fawn hooded rats (FHR), a strain of rat with a hereditary bleeding tendency due to a genetic defect in platelet aggregation, have recently been found to develop pulmonary hypertension. However, whether the pulmonary hypertension in FHR has a genetic basis or simply reflects the influence of extrinsic factors known to increase pulmonary artery pressure in other rat strains has not been fully evaluated. To further examine the structural and hemodynamic changes of pulmonary hypertension in FHR, and to investigate the extent to which alveolar hypoxia may have promoted these abnormalities, hemodynamic and morphometric measurements were made in FHR (4 to 24 wk) and compared with age-matched Sprague-Dawley (SDR) control rats. Increases in mean pulmonary artery pressure, total pulmonary resistance, and right ventricular enlargement were present in both male and female FHR and were evident at an early age (4 wk). Morphometric analysis of barium gelatin-infused lungs revealed marked pulmonary vascular remodelling in FHR characterized as extension of muscle into more peripheral pulmonary vessels, medial hypertrophy of proximal vessels, and reduced number of barium-filled arteries. The increases in pulmonary artery pressure in FHR were not due to the influence of more severe hypoxia, hypoventilation, or polycythemia, as blood gas tension and hematocrit were similar in FHR and SDR. Moreover, we found that pulmonary hypertension could be transmitted to backcross and second filial generation offspring arising from selective matings between FHR and control Wistar Kyoto rats, confirming the heritable basis for pulmonary hypertension in the FHR.

Animals↗
PubMed1991

Vascular cell responses to a hybrid transforming growth factor-beta molecule.

Functional biological assays were performed using a hybrid molecule of Transforming Growth Factor-Beta (TGF-5 beta) where nine amino acids near the cleavage site of TGF-beta 1 were substituted with nine amino acids located in the identical position of TGF-beta 2. Bovine aortic endothelial and smooth muscle cells as well as rat epididymal fat pad microvascular endothelia were studied in three distinct bioassays examining proliferation, migration and angiogenesis. The data suggested TGF-5 beta elicited results that do not differ significantly from the TGF-beta 1 isoform, while TGF-beta 2 expressed unique characteristics. We have also shown that these amino acid substitutions to TGF-beta 1 do not, in fact, alter the biological functions of the growth factor.

Animals↗
PubMed1991

DNA sequence analysis of X-ray induced Adh null mutations in Drosophila melanogaster.

The mutational spectrum for 28 X-ray induced mutations and 2 spontaneous mutations, previously determined by genetic and cytogenetic methods, consisted of 20 multilocus deficiencies (19 induced and 1 spontaneous) and 10 intragenic mutations (9 induced and 1 spontaneous). One of the X-ray induced intragenic mutations was lost, and another was determined to be a recombinant with the allele used in the recovery scheme. The DNA sequence of two X-ray induced intragenic mutations has been published. This paper reports the results of DNA sequence analysis of the remaining intragenic mutations and a summary of the X-ray induced mutational spectrum. Only one of the X-ray induced mutations is a single base change, a C to G transversion (AdhnLA80). Therefore, the mutational spectrum of X-ray induced mutations consists predominantly of deletions that are observed to range in size from two base pairs to deletions of a large number of loci as determined by genetic complementation analysis. The combination of DNA sequence analysis with genetic complementation analysis shows a continuous distribution in size of deletions rather than two different types of mutations consisting of deletions and "point mutations." Sequencing is shown to be essential for detecting intragenic deletions. Of particular importance for future studies is the observation that all of the intragenic deletions consist of a direct repeat adjacent to the break-point with one of the repeats deleted.

Alcohol Dehydrogenase↗
PubMed1991

Iron supplementation and running performance in female cross-country runners.

The purpose of this study was to determine the effects of two weeks of high dosage iron supplementation on various blood iron indices and metabolic parameters in non-anemic, iron-depleted competitive female cross-country runners. The subjects were highly trained members of the Colorado State University cross-country team and were completing 40 to 50 miles of training weekly. A pretest, post-test single-blind crossover design was employed. Upon collection of baseline exercise blood and metabolic data, five subjects were randomly assigned to iron supplementation (650 mg ferrous sulfate; 130 mg elemental iron) and five subjects to placebo treatment. At two weeks the treatments were reversed. Exercise blood and metabolic data were collected at two-week intervals. Dietary iron intake was assessed using a three-day dietary survey. Dietary analysis revealed deficiencies in vitamin B-6, iron, magnesium, and zinc according to USRDA standards. Baseline blood samples revealed no deficiencies in iron storage or transport proteins. Two weeks of iron supplementation resulted in no significant increases in blood iron indices. Metabolic parameters related to running performance were also unchanged after iron supplementation. High dosage, short-term iron supplementation appears to have no effect on blood or metabolic parameters in iron-depleted but non-anemic female cross-country runners.

Adult↗
PubMed1991

Vascular cell responses to TGF-beta 3 mimic those of TGF-beta 1 in vitro.

The vascular cell responses to the type 3 isoform of transforming growth factor-beta (TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMCs) as well as rat epididymal fat pad microvascular endothelia (RFCs). Four distinct bioassays indicated that TGF-beta 3 elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. Inhibition of proliferation by TGF-beta 3 at a 5-day time point ranged from 85% on BAECs, to 55% and 53% on RFCs and BASMCs, respectively. The effects of TGF-beta 3 and TGF-beta 1 on cell migration were also found to be similar; migration of large vessel endothelial cells was inhibited 35%, while migration of smooth muscle cells was enhanced 30%. TGF-beta 1 and TGF-beta 3 also had equivalent effects on neovascularization while a 10-fold higher concentration of TGF-beta 2 was required to elicit a similar response. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent upon the cell type examined. In summary, both the TGF-beta 1 and TGF-beta 3 isoforms of the transforming growth factor-beta family evoke comparable responses in proliferation, migration, angiogenic and cell surface binding assays using three distinct vascular cell types, while the biofunctions of TGF-beta 2 on these cells are distinct.

Animals↗