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Biomedical subjects

T Boone

Publications and source records attributed to T Boone.

At least 73 records · Page 4Linked to original sources

Cardiorespiratory and hemodynamic responses to inversion and inversion with sit-ups.

Eighteen men were studied during 15 minutes of inversion to determine the effects of 4 sit-ups per minute for 5 minutes on the cardiorespiratory system. Systolic blood pressure, diastolic blood pressure, ventilation, oxygen uptake, and METS increased significantly from preinversion/standing (A) to inversion (B). Arterial blood pressure increased from 122/81 mmHg to 142/99 mmHg during the first 5 minutes of inversion. Oxygen uptake increased from 341 ml.min-1 to 456 ml.min-1. Heart rate decreased significantly from (A) to (B). Double product, frequency of breaths, and tidal volume were not significantly changed from (A) to (B). Blood pressure, double product, ventilation, frequency of breaths, oxygen uptake, and METS increased significantly from the first 5 minutes of inversion (B) to the second 5 minutes of inversion with sit-ups (C). Arterial blood pressure increased from 142/99 mmHg (B) to 163/104 mmHg (C). The diastolic value remained significantly increased following the muscle strengthening exercise. Double product increased from 104 (B) to 126 (C), and oxygen uptake increased from 456 ml.min-1 (B) to 565 ml.min-1 (C). Following inversion/sit-ups (C), oxygen uptake decreased significantly during the third 5 minutes of inversion (D). Systolic blood pressure was also significantly decreased at (D) following the sit-ups. Upon returning to the standing position (E) versus the third 5 minutes of inversion (D), arterial blood pressure decreased significantly from 151/108 mmHg (D) to 123/84 mmHg (E). The postinversion/standing (E) blood pressure was nonsignificantly different from the preinversion/standing (A) blood pressure as was also the case with heart rate, double product, and tidal volume. Ventilation, frequency of breaths, oxygen uptake, and METS were still significantly increased during (E) versus (A). These data illustrate the influence of muscular exercise on the cardiorespiratory system during full -90 degree inversion. The increase in blood pressure is no cause for concern, and the assumed dangerous effects of full inversion have been overestimated.

Adolescent↗

Cardiovascular and thermal responses of triathlon performance.

Triathletes typically train each triathlon event separately. Therefore, to determine the cardiovascular and thermal differences between training and triathlon performance, nine male triathletes performed a simulated 75-min (40 km) control bike and a 40-min (10 km) control run at 70% of maximal oxygen uptake. Control data were compared to data derived from a simulated triathlon (0.8-km swim, 75-min bike, and 40-min run). Results demonstrated that prior swimming significantly decreased (P less than 0.05) triathlon cycling work output (191 +/- 4.2 to 159 +/- 7.6 W) producing mean differences (P less than 0.05) in oxygen uptake (3.18 +/- 0.1 to 3.01 +/- 0.11.min-1), ventilation (84.7 +/- 4 to 80.4 +/- 4.21.min-1), stroke volume (128 +/- 7.1 to 118 +/- 3.5 ml.min-1), cardiac output (20.7 +/- 1.2 to 18.9 +/- 0.8 l.min-1), mean arterial pressure (105 +/- 3.8 to 96 +/- 7.9 mm Hg) and rectal temperature (38.2 +/- 0.2 to 38.4 +/- 0.3 degrees C). Triathlon running, while performing identical control work output, elicited significant increases (P less than 0.05) in oxygen uptake (3.41 +/- 0.1 to 3.85 +/- 0.1 l.min-1), ventilation (91.3 +/- 3.3 to 104.2 +/- 2.8 l.min-1), heart rate (161 +/- 3.1 to 174 +/- 3.6 beats.min-1), arteriovenous oxygen difference (15.3 +/- 0.2 to 17.2 +/- 0.3 ml.100 ml-1) and rectal temperature (38.3 +/- 0.2 and 39.2 +/- 0.3 degrees C) with significantly lower (P less than 0.05) stroke volume (138 +/- 2.4 to 129 +/- 3.6 ml.min-1) and mean arterial pressure (102 +/- 11.2 to 89 +/- 5.5 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Construction, purification and biological activities of recombinant human interleukin-2 analogs.

Fourteen human interleukin-2 (IL-2) analogs have been cloned and expressed in E. coli, starting from a chemically synthesized gene for human IL-2 optimized for expression in E. coli. These analogs were purified to greater than 95% purity as determined by SDS-PAGE, and were measured for biological activity in a 3H-thymidine incorporation assay using an IL-2 dependent murine T-cell line (CTLL). One analog was made which eliminated the N-terminal 23 amino acids from the protein by replacing one restriction endonuclease fragment with another. This analog, which begins at an internal methionine, had no detectable CTLL activity. Thirteen analogs were constructed using oligonucleotide site-directed mutagenesis. Four of these analogs were truncated at various residues near the C-terminus (residues 106, 116, 121 and 126). These analogs had at least 500-fold lower CTLL activities than the natural recombinant IL-2. The remaining nine analogs had substitutions at 1, 2, or all 3 of the three cysteine residues in the protein (residues 58, 105 and 125). Substituting an alanine, asparagine, aspartic acid, or serine at residue 125 resulted in highly active molecules with CTLL activities similar to that of the natural recombinant IL-2. The analogs with alanine and serine substitutions at residue 125 actually had slightly higher CTLL activities than the natural recombinant IL-2. Substituting alanine for cysteine at position 125 and serine for cysteine at either position 58 or 105 yielded analogs with about 150-fold lower CTLL activities than natural recombinant IL-2. Substituting an alanine for the cysteine at position 125 and serines for cysteines at both positions 58 and 105 resulted in an analog with 30-fold lower CTLL activity than the natural recombinant IL-2. The ten analogs with less than 1.0% of the CTLL activity of natural recombinant IL-2 were tested for competition with the natural recombinant IL-2 by mixing a 10-to 100- fold excess of the analog with the natural recombinant IL-2 and assaying the mixture in the CTLL assay. None of these analog mixtures resulted in a lower activity than mixing the natural recombinant IL-2 with buffer alone, implying that none of these analogs effectively competes with the natural recombinant IL-2 for binding to IL-2 receptors during incubation with the CTLL cells. If reduced binding does occur, it may be the direct cause of their lower activities.

Amino Acid Sequence↗

Postinversion responses to inversion in normal subjects.

The purpose of this study was to determine cardiac output and related cardiovascular responses during postinversion by comparing preinversion (baseline data) to postinversion data in healthy, normal subjects. Each of 20 subjects (means = 22 years) was inverted for five minutes. Cardiac output was measured noninvasively with the Beckman MMC and CO2 rebreathing program. ANOVA with repeated measures was used to determine significance of change between preinversion and postinversion values. The alpha level was set at 0.05 for statistical significance. During postinversion stand, there were (a) significant decreases in oxygen uptake (p less than 0.0008), cardiac output (p less than 0.0005), and stroke volume (p less than 0.0018); (b) significant increases in arteriovenous oxygen difference (p less than 0.0281), peripheral vascular resistance (p less than 0.0001), and diastolic blood pressure (p less than 0.0087); and (c) nonsignificant changes in heart rate, systolic blood pressure, and double product from the preinversion baseline standing position. The results demonstrate little if any need for concern for a subject's return to the upright position.

Adult↗

Three-dimensional structure of interleukin-2.

Interleukin-2 is an effector protein that participates in modulating the immune response; it has become a focal point for the study of lymphokine structure and function. The three-dimensional structure of the interleukin molecule has been solved to 3.0 angstrom resolution. Interleukin-2 has a novel alpha-helical tertiary structure that suggests one portion of the molecule forms a structural scaffold, which underlies the receptor binding facets of the molecule.

Animals↗

Crystals and a low resolution structure of interleukin-2.

Recombinant derived human interleukin-2 and an analog in which cysteine 125 has been replaced with alanine have been crystallized in a form suitable for x-ray diffraction. The crystals are triclinic, space group P1, with two protein molecules in the unit cell; unit cell parameters are a = 55.8 A, b = 40.1 A, c = 33.7 A, alpha = 90.0 degrees, beta = 109.3 degrees, gamma = 93.2 degrees. The interleukin-2 structure has been solved to 5.5 A resolution using heavy atom isomorphous replacement methods. The resultant low resolution model reveals a significant fraction of alpha helical secondary structure and outlines the overall tertiary structure of the molecule.

Crystallization↗

Structure of unfolded and refolded recombinant derived [Ala125]interleukin 2.

Naturally occurring interleukin 2 (IL-2) contains an odd number (three) of cysteinyl residues and thus is susceptible to the formation of a variety of intramolecular and intermolecular disulfide bonds. The cysteine at residue 125 has been replaced with an alanine residue by site-directed mutagenesis, and hence, this analogue can form only one intrachain disulfide bond. When expressed at high levels in Escherichia coli, this recombinant DNA derived IL-2 analogue is insoluble, reduced, and inactive. The protein was solubilized by denaturants and, after purification, was oxidized to form an intramolecular disulfide bond. Circular dichroism (CD) has been used to investigate the effects of various denaturants on the unfolding-refolding process of the purified, oxidized protein. A similar conformation is obtained when [Ala125]interleukin 2 [IL-2(Ala-125)] is refolded from 6 M guanidine hydrochloride, 8 M urea, or 5% acetic acid. The resultant protein, refolded from these denaturants, is monomeric and has activity comparable to or greater than that reported for naturally derived IL-2. In addition to this form, aggregates, as evidenced from gel filtration, are obtained. The specific activities of these are greatly reduced, and CD spectra indicated that they have much less helical content than the monomeric form of the protein. CD spectra also showed that the tertiary structure of IL-2(Ala-125) is entirely different in the presence of sodium dodecyl sulfate (SDS) from that of the monomeric form in the absence of SDS.

Acetates↗

Parameters for the evaluation of IL-2 stability.

Recombinant DNA derived interleukin-2 stability in accelerated and long term studies was evaluated using biological and protein chemical methods. Various biophysical parameters were investigated for their correlation with bioassay results and for their accuracy and utility as quantitative indicators of change. Biochemically distinguishable forms of the molecule exhibited different levels of IL-2 activity in vitro. Of the methods evaluated, SDS-PAGE and, to a greater extent, reverse phase and TSK based HPLC analyses have been found to measure relevant changes in the structure of human interleukin-2. Those test systems detect covalent and non-covalent aggregates, degradation products, and inappropriately oxidized forms of human interleukin-2 all of which contribute to an overall loss of IL-2 biological activity. Such measures provide sensitive and reproducible indications of changes relative to the standard bioassay. These studies have led to the development of an analog of interleukin-2 which is biologically active and shows improved long term stability.

Biological Assay↗

Carotid palpation at two exercise intensities.

It remains unclear whether carotid palpation (CP) should be used to count post-exercise heart rate (HR). We hypothesized that the carotid sinus, when stretched or compressed by external pressure, results in an increased nerve activity to the cardiovascular areas in the brain stem, with a resultant increase in parasympathetic activity and a decrease in sympathetic activity. The primary purpose of this study was to investigate the effects of CP and no CP on post-exercise HR determination at two exercise intensities. The secondary purposes were to investigate whether CP during exercise would elicit a decrease in HR and the effects of CP on post-exercise blood pressure. Twenty-one healthy females served as subjects. During the final min of each exercise intensity, two 10-s HRs were recorded by continuous ECG (i.e., 10 s without palpation and 10 s with palpation). Immediately post-exercise at each intensity, the carotid artery was either palpated (Phase I) or not palpated (Phase II). At 60 and 80% intensity, with 10-s CP, post-exercise HR decreased 12.4 and 7 beats . min-1, respectively (both were significant: P less than 0.05). At 60 and 80% intensity, without CP, post-exercise HR decreased 6.1 and 3.3 beats . min-1 in 10-s, respectively (both were significant; P less than 0.05). CP during exercise did not elicit a carotid sinus reflex, and post-exercise CP did not alter blood pressure readings. These findings were generally contrary to previous research on CP and were determined to be important in that the correct technique was used by the investigators.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dissimilarities between purified human interleukin-1 and recombinant human interleukin-2 in the induction of fever, brain prostaglandin, and acute-phase protein synthesis.

The lymphokine interleukin-2 (IL-2) has been shown to enhance natural cell-mediated cytotoxicity, the generation of cytolytic T lymphocytes, and several other aspects of cellular immune function. The gene coding for human IL-2 has been cloned, and recombinant IL-2 will be available for clinical trials in patients with neoplastic, infectious, and immunodeficiency diseases. The present investigation was undertaken to determine if IL-2 was similar to interleukin-1 (IL-1) in its ability to induce fever and the acute-phase response. These studies were based on recent work with recombinant human interferon (IFN)-alpha, which is intrinsically pyrogenic and capable of producing fever by inducing the synthesis of prostaglandin E2 (PGE2). The prospect that IL-2 might exert similar physiologic effects is of critical concern since elevated temperature, PGE2, and acute-phase reactants may profoundly inhibit natural cell-mediated cytotoxicity. Our studies have shown that recombinant human IL-2 is not intrinsically pyrogenic in rabbits at doses as high as 10,000 units/kg when administered by a single intravenous injection. In contrast to IL-1, IL-2 does not stimulate cultured hypothalamus cells to synthesize PGE2, and, furthermore, IL-2 does not elevate serum C-reactive protein levels. These results predict that the administration of IL-2 to patients in doses that stimulate cellular immune function will not induce fever and other toxic side effects frequently seen in individuals receiving IFN.

Animals↗

Rescue of anti-influenza A virus cytotoxic T-lymphocyte responses in chemotherapy-suppressed mice.

The administration of cyclophosphamide (50 to 100 mg/kg) at 48 to 72 h before removal of murine lung or spleen mononuclear cells for culture rendered DBA/2 mice incapable of generating an effective cytotoxic T-lymphocyte response to influenza A virus-infected cells. The cytotoxic T-lymphocyte precursor frequency to influenza A virus in lung and spleen cells from cyclophosphamide-treated mice was significantly decreased when compared with that of normal littermate controls. The low cytotoxic T-lymphocyte activity in the lungs and spleens of cyclophosphamide-treated mice could be partially restored in vitro by human interleukin 2.

Animals↗

Carotid palpation and heart rate changes in postmyocardial infarction patients.

Forty cardiac rehabilitation patients were selected to determine the effects of carotid artery palpation at different time periods during rest, exercise, and recovery on the bicycle ergometer and following jogging-in-place. Fifteen-second carotid artery palpation was performed twice during minutes 1 and 3. The experimenter palpated during minute 1 while the subject palpated during minute 3. A significant decrease in resting heart rate occurred during minute 1 when the experimenter palpated, but no significance was evident during minute 3 when the subject palpated. During exercise with experimenter palpation, a significant decrease in HR occurred during the second 15 seconds of minute 1. Subject palpation during minute 3 did not significantly influence exercise heart rate. Both experimenter and subject palpation during minutes 1 and 3, respectively, of recovery 1 (on the bike) resulted in significant decrease in recovery heart rate. Jogging-in-place (recovery 2) was not influenced by experimenter or subject palpation. The significance of these findings lies in the fact that, although carotid palpation had a significant influence on heart rate, the differences were too small to be determined by a 10- or 15-second count. Thus, carotid palpation cannot be considered a threat to the postmyocardial infarction patient's safety.

Carotid Arteries↗

Perforation of the cecum, as a complication of pleural biopsy.

A case of a rupture of the cecum following pleural biopsy in a patient with lung carcinoma complicated by inappropriate secretion of antidiuretic hormone is reported. We hypothesized that this unusual complication was caused by a neurogenic effect caused by the trauma of the biopsy causing an imbalance in the autonomic nervous system producing a sympathetic predominance leading to adynamic ileus and subsequent perforation.

Aged↗